scholarly journals Novel GC-MS/MS Technique Reveals a Complex Steroid Fingerprint of Subclinical Hypercortisolism in Adrenal Incidentalomas

2019 ◽  
Vol 104 (8) ◽  
pp. 3545-3556 ◽  
Author(s):  
Václav Hána ◽  
Jana Ježková ◽  
Mikuláš Kosák ◽  
Michal Kršek ◽  
Václav Hána ◽  
...  
Keyword(s):  
Wide Spectrum ◽  
Serum Cortisol ◽  
Serum Levels ◽  
Dehydroepiandrosterone Sulfate ◽  
Urinary Free Cortisol ◽  
Cross Sectional Study ◽  
Adrenal Incidentalomas ◽  
Subclinical Hypercortisolism ◽  
Cross Sectional ◽  
Free Cortisol

AbstractContextImprovement of imaging methods has led to more incidental adrenal tumor findings, especially adenomas. Routine hormonal evaluation uses only a few steroids to evaluate possible hormonal hypersecretion of these adenomas, but a wide spectrum of serum steroid hormone changes has not been published.ObjectiveTo measure the serum levels of 83 steroids from patients with unilateral and bilateral adrenal incidentalomas to uncover full steroid profile changes in patients with subclinical hypercortisolism (SH).DesignCross-sectional study.SettingThe study was conducted at a tertiary inpatient clinic.PatientsFifty-two patients with adrenal incidentalomas (unilateral, n = 29; bilateral, n = 23), including nonfunctioning (n = 11) vs SH (n = 41), and 26 age- and sex-matched controls from the general population were included.Main Outcome MeasuresEighty-three serum steroids were measured by gas chromatography–tandem mass spectrometry (GC-MS/MS) before and after 1 mg dexamethasone, ACTH, midnight serum cortisol, and urinary free cortisol/24 hour.ResultsOf 83 measured steroids, 10 were significantly decreased in patients with SH, including dehydroepiandrosterone sulfate (DHEAS), androsterone sulfate, epiandrosterone sulfate, androstenediol sulfate, conjugated 5α-androstane-3β,17β-diol, and conjugated 5α-androstane-3α,17β-diol. This finding was observed even when unilateral, bilateral, male, and female subgroups were analyzed separately. When we compared routine clinical methods and GC-MS/MS‒measured steroids, the most discriminatory was DHEAS followed by midnight serum cortisol, epiandrosterone sulfate, androsterone sulfate, ACTH, and 16α-hydroxypregnenolone.ConclusionsSH was associated with decreased levels of adrenal androgens, their metabolites, and pregnenolone metabolite. GC-MS/MS is a powerful tool for measuring serum levels of these undescribed changes in steroid metabolism, which are characteristic of SH in adrenal incidentalomas.

scholarly journals Clozapine Use Presenting with Pseudopheochromocytoma in a Schizophrenic Patient: A Case Report

2013 ◽  
Vol 2013 ◽  
pp. 1-3 ◽  
Author(s):  
Jaskanwal Sara ◽  
Matt Jenkins ◽  
Tanveer Chohan ◽  
Karan Jolly ◽  
Lisa Shepherd ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Adrenal Glands ◽  
Serum Cortisol ◽  
Serum Levels ◽  
Urinary Free Cortisol ◽  
Free Cortisol ◽  
History Of ◽  
Caucasian Female ◽  
Abnormal Uptake ◽  
Noradrenaline Levels

Introduction. There have been six previous cases that reported pseudopheochromocytoma in patients taking clozapine. Our case showed the direct link of clozapine to serum levels of certain markers.Case. This is a case of a 49-year-old obese Caucasian female who was referred to endocrinology for investigation of Cushing’s syndrome, based on raised blood pressure and Cushingoid facies. The patient had underlying schizophrenia and was stable on clozapine. Her blood pressure was 150/99 mmHg on bendroflumethiazide and candesartan. We measured her 24-hour urinary-free cortisol, which was normal but 24-hour urinary-free noradrenaline was elevated at 835 nmol (76–561) with normal adrenaline 36 nmol (7–82) and dopamine 2679 nmol (366–2879), as the patient had history of palpitations and sweating. Two sets of 24-hour urinary-free cortisol measurements were normal and serum cortisol suppressed to <50 nmol/l after a 1 mg overnight dexamethasone. Two further 24-hour urinary-free catecholamines showed a raised level of noradrenaline. MRI demonstrated normal adrenals and MIBG scan did not show any abnormal uptake at adrenal glands.Conclusion. Pseudopheochromocytoma has been reported in patients taking clozapine. A number of different mechanisms for raised plasma noradrenaline levels with clozapine have been postulated. The above case highlights an unusual but known side effect of clozapine.

scholarly journals Bilateral and unilateral adrenal incidentalomas: biochemical and clinical characteristics

2013 ◽  
Vol 168 (2) ◽  
pp. 235-241 ◽  
Author(s):  
V Morelli ◽  
S Palmieri ◽  
A S Salcuni ◽  
C Eller-Vainicher ◽  
E Cairoli ◽  
...  
Keyword(s):  
Serum Cortisol ◽  
Urinary Free Cortisol ◽  
Adrenal Incidentalomas ◽  
Mineral Density ◽  
Femoral Bone Mineral Density ◽  
Free Cortisol ◽  
Suppression Test ◽  
Cortisol Levels ◽  
Dexamethasone Suppression

ObjectiveThe possible different prevalence of arterial hypertension (AH), type 2 diabetes mellitus (T2DM), dyslipidaemia (DL) and vertebral fractures (FX) between patients with bilateral and unilateral adrenal incidentalomas (BAI and UAI, respectively) with and without subclinical hypercortisolism (SH) is unknown. In this study we compared the prevalence of AH, T2DM, DL and FX in BAI and UAI patients in relation to SH.DesignProspective study.MethodsIn 175 UAI and 38 BAI patients, we evaluated BMI, spinal and femoral bone mineral density (LS and FN BMD, respectively) and the presence of AH, T2DM, DL and FX. SH was diagnosed in the presence of ≥2 of the following: urinary free cortisol levels >193 nmol/24 h, serum cortisol levels after 1 mg dexamethasone suppression test >83 nmol/l or ACTH levels <2.2 pmol/l.ResultsAge, BMI and cortisol secretion were comparable, while FN BMD was lower in BAI than in UAI patients (−0.45±0.86 vs 0.09±1.07, P=0.004). The prevalence of SH, AH, T2DM, and DL was comparable, while the prevalence of FX was higher in BAI than in UAI (52.6 vs 28%, P=0.007). The presence of FX was associated with BAI (odds ratio (OR) 2.6, 95% confidence interval (95% CI) 1.2–5.6, P=0.016), after adjusting for SH (OR 1.77, 95% CI 0.85–3.7, P=0.12), BMI (OR 1.06, 95% CI 0.98–1.13, P=0.1), age (OR 1.07, 95% CI 1.04–1.11, P=0.0001) and LS BMD (OR 1.31, 95% CI 1.03–1.67, P=0.03).ConclusionBAI patients have an increased FX risk than UAI ones. Further studies should investigate the causes of bone involvement in BAI patients.

scholarly journals Biochemical and clinical benefits of unilateral adrenalectomy in patients with subclinical hypercortisolism and bilateral adrenal incidentalomas

2015 ◽  
Vol 173 (6) ◽  
pp. 719-725 ◽  
Author(s):  
I Perogamvros ◽  
D A Vassiliadi ◽  
O Karapanou ◽  
E Botoula ◽  
M Tzanela ◽  
...  
Keyword(s):  
Serum Cortisol ◽  
Adrenal Incidentalomas ◽  
Plasma Acth ◽  
Subclinical Hypercortisolism ◽  
Unilateral Adrenalectomy ◽  
Early Results ◽  
Number Of Patients ◽  
Free Cortisol ◽  
Surgical Group

ObjectiveThe treatment of subclinical hypercortisolism in patients with bilateral adrenal incidentalomas (AI) is debatable. We aimed to compare the biochemical and clinical outcome of unilateral adrenalectomy vs a conservative approach in these patients.DesignRetrospective study.MethodsThe study included 33 patients with bilateral AI; 14 patients underwent unilateral adrenalectomy of the largest lesion (surgical group), whereas 19 patients were followed up (follow-up group). At baseline and at each follow-up visit, we measured 0800 h plasma ACTH, midnight serum cortisol (MSF), 24-h urinary-free cortisol (UFC) and serum cortisol following a standard 2-day low-dose-dexamethasone-suppression test (LDDST). We evaluated the following comorbidities: arterial hypertension, impaired glucose tolerance or diabetes mellitus, dyslipidemia and osteoporosis.ResultsBaseline demographic, clinical characteristics and the duration of follow-up (53.9±21.3 vs 51.8±20.1 months, for the surgical vs the follow-up group) were similar between groups. At the last follow-up visit the surgical group had a significant reduction in post-LDDST cortisol (2.4±1.6 vs 6.7±3.9 μg/dl,P=0.002), MSF (4.3±2 vs 8.8±4.6 μg/dl,P=0.006) and 24-h UFC (50.1±21.1 vs 117.9±42.4 μg/24 h,P=0.0007) and a significant rise in mean±s.d.morning plasma ACTH levels (22.2±9.6 vs 6.9±4.8 pg/ml,P=0.002). Improvement in co-morbidities was seen only in the surgical group, whereas no changes were noted in the follow-up group.ConclusionsOur early results show that removal of the largest lesion offers significant improvement both to cortisol excess and its metabolic consequences, without the debilitating effects of bilateral adrenalectomy. A larger number of patients, as well as a longer follow-up, are required before drawing solid conclusions.

scholarly journals Plasma Steroid Metabolome Profiling for Diagnosis and Subtyping Patients with Cushing Syndrome

2018 ◽  
Vol 64 (3) ◽  
pp. 586-596 ◽  
Author(s):  
Graeme Eisenhofer ◽  
Jimmy Masjkur ◽  
Mirko Peitzsch ◽  
Guido Di Dalmazi ◽  
Martin Bidlingmaier ◽  
...  
Keyword(s):  
Cushing Syndrome ◽  
Urinary Free Cortisol ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Free Cortisol ◽  
Multistep Process ◽  
Steroid Profiles ◽  
Plasma Steroids ◽  
Metabolome Profiling ◽  
Adrenal Disease

Abstract BACKGROUND Diagnosis of Cushing syndrome requires a multistep process that includes verification of hypercortisolism followed by identification of the cause of adrenocortical hyperfunction. This study assessed whether pituitary, ectopic, and adrenal subtypes of Cushing syndrome were characterized by distinct plasma steroid profiles that might assist diagnosis. METHODS In this retrospective cross-sectional study, mass spectrometric measurements of a panel of 15 plasma steroids were applied to 222 patient samples tested for Cushing syndrome. Disease was excluded in 138 and confirmed in 51 patients with pituitary Cushing syndrome, 12 with ectopic adrenocorticotropin secretion, and 21 with adrenal disease. Another 277 age- and sex-matched hypertensive and normotensive volunteers were included for comparison. RESULTS Compared with patients without disease, the largest increases in plasma steroids among patients with Cushing syndrome were observed for 11-deoxycortisol (289%), 21-deoxycortisol (150%), 11-deoxycorticosterone (133%), corticosterone (124%), and cortisol (122%). Patients with ectopic disease showed the most prominent increases, but there was considerable variation for other steroids according to subtype. Patients with adrenal disease had the lowest concentrations of androgens, whereas those with ectopic and pituitary disease showed the lowest concentrations of aldosterone. Plasma 18-oxocortisol was particularly low in ectopic disease. With the use of 10 selected steroids, subjects with and without different Cushing syndrome subtypes could be discriminated nearly as closely as with the use of salivary and urinary free cortisol, dexamethasone-suppressed cortisol, and plasma adrenocorticotropin (9.5% vs 5.8% misclassification). CONCLUSIONS Patients with different subtypes of Cushing syndrome show distinctive plasma steroid profiles that may offer a supplementary single-test alternative for screening purposes.

scholarly journals Biochemical screening for subclinical cortisol-secreting adenomas amongst adrenal incidentalomas

2001 ◽  
pp. 401-408 ◽  
Author(s):  
N Valli ◽  
B Catargi ◽  
N Ronci ◽  
V Vergnot ◽  
F Leccia ◽  
...  
Keyword(s):  
Diurnal Variation ◽  
Screening Test ◽  
Serum Cortisol ◽  
Biochemical Parameter ◽  
Urinary Free Cortisol ◽  
Cortisol Concentration ◽  
Cortisol Secretion ◽  
Adrenal Incidentalomas ◽  
Free Cortisol ◽  
Biochemical Abnormalities

OBJECTIVE: Biochemistry and I-6beta-iodomethyl norcholesterol scintigraphy (IMS) have both been used to assess cortisol secretion by adrenocortical incidentalomas. However, which biochemical abnormalities indicate subclinical corticoid excess is still debatable whilst IMS is expensive and cumbersome. The aim of the study was to evaluate prospectively patients with adrenal incidentalomas using both IMS and biochemical methods to examine whether the IMS pattern is associated with biochemical abnormalities and, if this is so, to find a biochemical parameter that could be used as a screening test to identify a subset of patients on whom IMS could subsequently be performed. METHODS: Thirty-one patients with benign cortical adenomas were recruited from 43 consecutive patients with adrenal incidentalomas. All 31 patients underwent IMS and measurement of (i) 0800 h serum cortisol, ACTH, dehydroepiandrosterone and 17-hydroxyprogesterone; (ii) midnight serum cortisol; (iii) 2400 h excretion of urinary free cortisol; (iv) cortisol after the overnight 1 mg dexamethasone (DEX) suppression test; (v) cortisol after an i.v. 4 mg DEX test; (vi) determination of the diurnal variation in serum cortisol. RESULTS: Sixty-one per cent of patients displayed unilateral uptake during IMS and 39% showed bilateral uptake. Patients with unilateral uptake exhibited significantly lower ACTH concentrations (P=0.0005), higher midnight cortisol concentrations (P=0.02), disrupted diurnal variation of serum cortisol (P=0.02) and higher cortisol concentrations after DEX suppression tests (P=0.01). Cortisol concentrations following the two DEX suppression tests correlated closely (r=0.80, P=0.0001). The i.v. 4 mg DEX test was clearly more sensitive for the diagnosis of unilateral uptake than the overnight 1 mg DEX test (76 vs 52%). Using various thresholds of cortisol concentration following the overnight 1 mg DEX test, it was found that the sensitivity of the test could be improved to 100% if the threshold was set at 60 nmol/l rather than the classical value of 138 nmol/l. All patients but one with post-test serum cortisol concentrations above 60 nmol/l as against none of patients with cortisol below 60 nmol/l exhibited at least one associated biochemical abnormality indicating subclinical glucocorticoid excess. CONCLUSION: In adrenocortical incidentalomas, unilateral uptake during IMS suggests subclinically excessive and/or autonomous cortisol secretion. A cortisol concentration above 60 nmol/l following the overnight 1 mg DEX test is highly correlated with unilateral uptake and is associated with biochemical abnormalities indicating subclinical glucocorticoid excess. Our results favour the use of the 1 mg overnight DEX test with revised criteria of interpretation as a screening test for subclinical hypercortisolism among patients with adrenocortical incidentalomas.

scholarly journals Adrenalectomy reduces the risk of vertebral fractures in patients with monolateral adrenal incidentalomas and subclinical hypercortisolism

2016 ◽  
Vol 174 (3) ◽  
pp. 261-269 ◽  
Author(s):  
Antonio Stefano Salcuni ◽  
Valentina Morelli ◽  
Cristina Eller Vainicher ◽  
Serena Palmieri ◽  
Elisa Cairoli ◽  
...  
Keyword(s):  
Vertebral Fractures ◽  
Serum Cortisol ◽  
Adrenal Incidentalomas ◽  
Mineral Density ◽  
Subclinical Hypercortisolism ◽  
X Ray ◽  
Increased Risk ◽  
Free Cortisol ◽  
Surgical Group

ObjectiveSubclinical hypercortisolism (SH) is associated with increased risk of vertebral fractures (VFx). The effect on bone following recovery from SH is unknown.DesignOf the 605 subjects consecutively referred for monolateral adrenal incidentalomas (AIs) to our outpatient clinics, 55 SH patients (recruited on the basis of the exclusion criteria) were enrolled. We suggested to all patients to undergo adrenalectomy, which was accepted by 32 patients (surgical group, age 61.3±8.1 years) and refused by 23 patients, who were followed with a conservative management (non-surgical group, age 65.4±7.1 years).MethodsWe diagnosed SH in patients with serum cortisol after 1 mg dexamethasone suppression test (1 mg-DST) >5.0 μg/dl or with greater than or equal to two criteria among 1 mg-DST >3.0 μg/dl, urinary free cortisol >70 μg/24 h and ACTH <10 pg/ml. We assessed: bone mineral density (BMD) at lumbar spine (LS) and femoral neck (as Z-score) by dual-energy X-ray absorptiometry and the VFx presence by X-ray at baseline and at the end of follow up (surgical group 39.9±20.9 months and non-surgical group 27.7±11.1 months).ResultsThe LS Z-score (ΔZ-score/year) tended to increase in the surgical group (0.10±0.20) compared with the non-surgical group (−0.01±0.27, P=0.08) and in the former, the percentage of patients with new VFx was lower (9.4%) than in the latter (52.2%, P<0.0001). Surgery in AI patients with SH was associated with a 30% VFx risk reduction (odds ratio 0.7, 95% CI 0.01–0.05, P=0.008) regardless of age, gender, follow up duration, 1 mg-DST, LS BMD, and presence of VFx at baseline.ConclusionIn patients with monolateral AI and SH, adrenalectomy reduces the risk of VFx.

scholarly journals The Occurrence of Subclinical Hypercortisolism and Osteoporosis in Patients with Incidentally Discovered Unilateral and Bilateral Adrenal Tumors

2016 ◽  
Vol 35 (4) ◽  
pp. 401-409
Author(s):  
Sanja Ognjanović ◽  
Djuro Macut ◽  
Milan Petakov ◽  
Valentina Elezović Kovačević ◽  
Tatjana Isailović ◽  
...  
Keyword(s):  
Serum Cortisol ◽  
Urinary Free Cortisol ◽  
Adrenal Tumors ◽  
Mineral Density ◽  
Subclinical Hypercortisolism ◽  
Similar Frequency ◽  
Free Cortisol ◽  
Adrenal Masses ◽  
Suppression Test ◽  
Cortisol Levels

SummaryBackground:Adrenal incidentalomas (AI) are clinically silent adrenal masses that are detected incidentally during imaging procedures performed for unrelated diseases. The aim of this study was to investigate the prevalence of subclinical hypercortisolism (SH) and associated co-morbidities in patients with unilateral AI (UAI) and bilateral AI (BAI).Methods:We evaluated 152 patients, 105 (69.1%) with UAI and 47 (30.9%) with BAI. SH was diagnosed in the presence of serum cortisol levels after 1 mg dexamethasone suppression test (DST) or after 2-day low-dose DST (LDDST) > 50 nmol/L with at least one of the following parameters: midnight serum cortisol > 208 nmol/L, 24-h urinary free cortisol > 245 nmol/24 h, or ACTH < 10 ng/L. Bone mineral density (BMD) was measured at lumbar spine (LS) and femoral neck (FN).Results:Age, BMI, and waist circumference were comparable, and diabetes, hypertension and dyslipidemia occurred with similar frequency in both groups. The overall prevalence of SH was 20.5% based on post-1 mg DST, and 20.0% based on post-LDDST cortisol levels, and it was more prevalent in BAI than UAI patients (31.1%vs15.2%, respectively, p=0.026). LS BMD was lower in BAI than in UAI patients (0.96±0.14vs0.87±0.15, p=0.002). There were no differences in FN BMD. The prevalence of osteoporosis was higher in BAI compared to UAI patients (37.1%vs15.9%, respectively, p=0.011).Conclusions:Patients with BAI had higher prevalence of SH and osteoporosis than those with UAI. Frequency of other co-morbidities was similar. This may be due to the higher degree of autonomous cortisol secretion or different tissue-specific sensitivity to glucocorticoids.

scholarly journals Plasma Steroid Profiles in Subclinical Compared With Overt Adrenal Cushing Syndrome

2019 ◽  
Vol 104 (10) ◽  
pp. 4331-4340 ◽  
Author(s):  
Jimmy Masjkur ◽  
Matthias Gruber ◽  
Mirko Peitzsch ◽  
Denise Kaden ◽  
Guido Di Dalmazi ◽  
...  
Keyword(s):  
Cushing Syndrome ◽  
Plasma Concentrations ◽  
Screening Method ◽  
Serum Cortisol ◽  
Dehydroepiandrosterone Sulfate ◽  
Cross Sectional Study ◽  
Biochemical Tests ◽  
Cross Sectional ◽  
Steroid Profiles ◽  
Plasma Steroids

Abstract Context Diagnosis of subclinical adrenal hypercortisolism is based on several tests of the hypothalamic-pituitary-adrenal axis to establish mild alterations of cortisol secretion and dysregulated cortisol physiology. Objective We assessed whether plasma steroid profiles might assist diagnosis of subclinical Cushing syndrome (SC). Design Retrospective cross-sectional study. Setting Two tertiary medical centers. Patients Of 208 patients tested for hypercortisolism, disease was excluded in 152 and confirmed in 21 with overt adrenal Cushing syndrome (AC) compared to 35 with SC. Another 277 age- and sex-matched hypertensive and normotensive volunteers were included for reference. Main Outcome Measures A panel of 15 plasma steroids was measured by mass spectrometry, with classification by discriminant analysis. Results Patients with SC had lower plasma concentrations of dehydroepiandrosterone and dehydroepiandrosterone-sulfate than subjects without SC (P < 0.05). The largest increases (P < 0.001) in plasma steroids among patients with SC were observed for 11-deoxycortisol and 11-deoxycorticosterone. Nevertheless, concentrations of 11-deoxycorticosterone, 11-deoxycortisol, and pregnenolone in patients with AC were higher (P < 0.05) than in those with SC. Patients with SC or AC could be distinguished from subjects without disease using this combination of steroids as precisely as with use of measurements of serum cortisol after administration of dexamethasone. The steroid combination provided superior diagnostic performance compared with each of the other routine biochemical tests. Conclusion Distinct plasma steroid profiles in patients with SC may provide a simple and reliable screening method for establishing the diagnosis.

scholarly journals Diurnal Salivary Cortisol in Sarcopenic Postmenopausal Women: The OsteoLaus Cohort

2021 ◽  
Author(s):  
Elena Gonzalez Rodriguez ◽  
Pedro Marques-Vidal ◽  
Bérengère Aubry-Rozier ◽  
Georgios Papadakis ◽  
Martin Preisig ◽  
...  
Keyword(s):  
Postmenopausal Women ◽  
Salivary Cortisol ◽  
Population Based ◽  
Cross Sectional Study ◽  
Body Composition Assessment ◽  
Cross Sectional ◽  
X Ray ◽  
Free Cortisol ◽  
Cortisol Levels ◽  
The Relationship

AbstractSarcopenia, similar to hypercortisolism, is characterized by loss of muscle mass and strength. Cortisol circadian rhythm changes with aging (blunted late-day nadir values) were suggested to contribute to this decline. We aimed to explore the relationship between diurnal salivary cortisol values and sarcopenia diagnosis and its components in postmenopausal women. This is a cross-sectional study within the OsteoLaus population-based cohort in Lausanne (Switzerland). Participants had a body composition assessment by dual X-ray absorptiometry (DXA), a grip strength (GS) measure, and salivary cortisol measures (at awakening, 30 min thereafter, 11 AM (sc-11AM) and 8 PM (sc-8PM)). Associations between salivary cortisol and sarcopenia diagnosed by six different criteria (based on appendicular lean mass (ALM) assessed by DXA, and muscle strength by GS), and its components, were analyzed. 471 women aged > 50 years (63.0 ± 7.5) were included. Various definitions identified different participants as sarcopenic, who consistently presented higher salivary cortisol at 11 AM and/or 8 PM. There were no associations between salivary cortisol levels and ALM measures, either absolute or after correction to height squared (ALM index) or body mass index. GS was inversely correlated to sc-11AM (r = − 0.153, p < 0.001) and sc-8PM (r = − 0.118, p = 0.002). Each 10 nmol/l increase of sc-11AM, respectively sc-8PM, was associated with a GS decrease of 1.758 (SE 0.472) kg, respectively 2.929 (SE 1.115) kg. In postmenopausal women, sarcopenia is associated with higher salivary cortisol levels at 11 AM and 8 PM. An increase of daily free cortisol levels in the physiological range could participate to sarcopenia development by decreasing muscle function in postmenopausal women.

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