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 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 Clinical features, risk of mass enlargement, and development of endocrine hyperfunction in patients with adrenal incidentalomas: a long-term follow-up study

Endocrine ◽  
2020 ◽  
Author(s):  
Pierpaolo Falcetta ◽  
Francesca Orsolini ◽  
Elena Benelli ◽  
Patrizia Agretti ◽  
Paolo Vitti ◽  
...  
Keyword(s):  
Adrenal Incidentaloma ◽  
Plasma Renin ◽  
Serum Cortisol ◽  
Urinary Free Cortisol ◽  
Endocrine Function ◽  
Adrenal Tumors ◽  
Hormonal Function ◽  
Free Cortisol ◽  
Hormonal Evaluation

Abstract Purpose To evaluate the risk of mass enlargement and endocrine function modification in patients with adrenal incidentaloma (AI). Methods In this retrospective study, we examined clinical and hormonal characteristics of 310 patients with AI (200 females and 110 males; age: 58.3 ± 12.9 years), followed up for a median (interquartile range) of 31.4 months (13.0–78.6) and evaluated for possible modification in adrenal mass size and hormonal function. The hormonal evaluation included morning serum cortisol and plasma ACTH at 8 a.m., aldosterone, plasma renin activity/direct renin concentration, and 24-h urine metanephrines/normetanephrines. One microgram overnight dexamethasone suppression test (DST) was performed. Autonomous cortisol secretion (ACS) was diagnosed in the presence of cortisol after 1 mg DST > 5 μg/dl (138 nmol/l) or >1.8 and ≤5 μg/dl (50–138 nmol/l) and at least one of the following: (i) low ACTH; (ii) increased 24-h urinary-free cortisol; (iii) absence of cortisol rhythm; and (iv) post-LDDST cortisol level > 1.8 μg/dl (50 nmol/l). When there was no biochemical evidence of adrenal hormonal hyperactivity, AIs were classified as nonfunctioning (NFAIs). The mass was considered significantly enlarged when the size increase was more than 20% and at least 5 mm compared to baseline. Results At diagnosis, NFAIs were found in 209 patients, while ACS and overt adrenal hyperfunction were diagnosed in 81 and 20 patients, respectively. During follow-up, 3.3% and 1.5% of patients with NFAI developed subtle and overt endocrine hyperfunction, respectively, while a significant mass enlargement was observed in 17.7% of all AIs. The risk of developing ACS was significantly higher in patients with adenoma >28 mm (hazard ratio [HR] 12.4; 95% confidence interval [CI], 2.33–66.52, P = 0.003), in those with bilateral adrenal tumors (HR: 5.36; 95% CI, 1.17–24.48, P = 0.030), and with low/suppressed ACTH values (HR: 11.2, 95% CI 2.06–60.77; P = 0.005). The risk of mass enlargement was lower for patients in the fourth quartile of body mass index than those in the first quartile (HR 0.33; 95% CI, 0.14–0.78; P = 0.012). Conclusions In patients with AI, the risk of developing hormonal hyperfunction and mass enlargement is overall low, although some tumor characteristics and anthropometric features might increase this risk. Taking account of all these aspects is important for planning a tailored follow-up in AI patients.

scholarly journals Decreased pituitary sensitivity to glucocorticoids in endurance-trained men

2001 ◽  
pp. 363-368 ◽  
Author(s):  
M Duclos ◽  
JB Corcuff ◽  
F Pehourcq ◽  
A Tabarin
Keyword(s):  
Hpa Axis ◽  
Low Dose ◽  
Urinary Free Cortisol ◽  
Test Results ◽  
O2 Uptake ◽  
Plasma Acth ◽  
Free Cortisol ◽  
Suppression Test ◽  
Cortisol Levels ◽  
Dexamethasone Suppression

OBJECTIVE: Muscular exercise induces hypothalamo-pituitary-adrenal (HPA) axis activation and when regularly repeated, as in endurance training, leads to HPA axis adaptation. To assess whether non-professional endurance-trained (ET) men with a substantial training load and no clinical or biological features of HPA axis overactivity can present subtle alterations of HPA axis sensitivity to glucocorticoid negative feedback, nine ET men were subjected to HPA axis testing using the dexamethasone-corticotrophin-releasing hormone (CRH) test. DESIGN: Nine endurance-trained men and eight healthy age-matched sedentary men were studied. Morning plasma cortisol and 24 h urinary free cortisol (UFC) were determined and a low dose dexamethasone suppression test (LDDST) was performed followed by CRH stimulation (dexamethasone-CRH test). RESULTS: After a day without physical exercise, at 0800 h, plasma ACTH and cortisol concentrations, and the 24 h UFC and UFC/urinary creatinine (UC) ratio were similar in ET and sedentary men. By contrast, clear differences between the groups were seen in cortisol and ACTH responses to the dexamethasone-CRH test. In eight ET subjects, after LDDST, basal ACTH and cortisol levels were similar to those of sedentary men, whereas one ET subject displayed a poor suppression of cortisol level (131 nmol/l). After injection of CRH, however, three of nine ET men's cortisol levels were not suppressed by dexamethasone but instead displayed significant CRH-induced increase (peak cortisol: 88, 125 and 362 nmol/l). No sedentary subject exhibited any increase in cortisol levels. CONCLUSION: Three of nine ET men with a mean maximum rate of O2 uptake (VO2, max) of 61 ml/kg per min, running 50-70 km per week, were resistant to glucocorticoid suppression during the combined dexamethasone-CRH test.

scholarly journals Defining Nonfunctioning Adrenal Adenomas on the Basis of the Occurrence of Hypocortisolism after Adrenalectomy

2020 ◽  
Vol 4 (8) ◽  
Author(s):  
Cristina Eller-Vainicher ◽  
Valentina Morelli ◽  
Carmen Aresta ◽  
Antonio Stefano Salcuni ◽  
Alberto Falchetti ◽  
...  
Keyword(s):  
Serum Cortisol ◽  
Urinary Free Cortisol ◽  
Tolerance Test ◽  
Cortisol Secretion ◽  
Unilateral Adrenalectomy ◽  
Insulin Tolerance ◽  
Free Cortisol ◽  
Suppression Test ◽  
Dexamethasone Suppression ◽  
Rule Out

Abstract Background In patients with adrenal incidentalomas (AIs), there is uncertainty on how to rule out hypercortisolism. The occurrence of postsurgical (unilateral adrenalectomy) hypocortisolism (PSH) has been proposed as a proof of the presence of presurgical hypercortisolism in AI patients. The aim of this study was to define the thresholds of cortisol level after the 1 mg overnight dexamethasone suppression test (F-1mgDST), urinary free cortisol (UFC), midnight serum cortisol (MSC), and adrenocorticotropin (ACTH) to predict the absence of PSH in AI patients undergoing surgery. Methods In 60 patients who underwent AI excision, cortisol secretion was assessed by a low-dose corticotropin stimulation test or insulin tolerance test when needed. We searched for the lowest presurgical value of F-1mgDST, UFC, and MSC and the highest value for ACTH in AI patients with PSH as indexes of normal cortisol secretion. Results The lowest values of F-1mgDST, UFC, and MSC and the highest value for ACTH in PSH patients were 1.2 µg/dL (33 nmol/L), 10.4 µg/24 hours (29 nmol/24 hours), 1.2 µg/dL (33 nmol/L), and 26.9 pg/mL (6 pmol/L), respectively, but only F-1mgDST &lt;1.2 µg/dL (33 nmol/L) was able to predict the absence of PSH. Among AI patients with F-1mgDST &lt;1.2 µg/dL (33 nmol/L) no subjects had diabetes mellitus and/or metabolic syndrome, and these subjects tended to have a better metabolic profile than those with F-1mgDST ≥1.2 µg/dL (33 nmol/L) Conclusion In AI patients a F-1mgDST &lt;1.2 µg/dL (33 nmol/L) rules out PSH and could be used to exclude hypercortisolism in AI patients.

Comparison of Salivary Cortisol, Serum Cortisol, Plasma ACTH and Urinary Free Cortisol Levels in Thyrotoxic and Hypothyroid Patients

2012 ◽  
Vol 32 (1) ◽  
pp. 54-58
Author(s):  
Mustafa Sait GÖNEN ◽  
Emin ÖZKAYA ◽  
Sevil KURBAN ◽  
Süleyman Hilmi İPEKCİ ◽  
Cevdet DURAN ◽  
...  
Keyword(s):  
Salivary Cortisol ◽  
Serum Cortisol ◽  
Urinary Free Cortisol ◽  
Plasma Acth ◽  
Free Cortisol ◽  
Cortisol Levels ◽  
Hypothyroid Patients

scholarly journals Ectopic ACTH Syndrome Emerging 5 Years after the Diagnosis of Neuroendocrine Tumor

2019 ◽  
Vol 2019 ◽  
pp. 1-5
Author(s):  
Minghao Liu ◽  
Diane Hamele-Bena ◽  
John Ausiello ◽  
Gabrielle Page-Wilson
Keyword(s):  
Neuroendocrine Tumor ◽  
Serum Cortisol ◽  
Urinary Free Cortisol ◽  
Ectopic Acth Syndrome ◽  
Ectopic Acth ◽  
Free Cortisol ◽  
Metastatic Lung ◽  
Suppression Test ◽  
Dexamethasone Suppression ◽  
Retrospective Examination

Ectopic ACTH syndrome (EAS) arising years after the diagnosis of a neuroendocrine tumor (NET) is exceedingly rare. We describe a case of EAS occurring five years after the diagnosis of a metastatic lung NET in a 61-year-old woman. She presented with severe hypokalemia but was not overtly Cushingoid on exam. Serum cortisol was 61mcg/dL after an overnight 1mg dexamethasone suppression test (<1.8mcg/dL) and urinary free cortisol was 7544 mcg/24h (<45mcg/24h), establishing the diagnosis of Cushing’s syndrome. Plasma levels of peptides which have been associated with EAS, Agouti-related peptide (AgRP) and the ACTH precursors POMC (31-kDa) and pro-ACTH (22-kDa), were elevated. Metyrapone was initiated, but hypercortisolism persisted and the patient succumbed to pneumonia shortly after presentation. Retrospective examination of biopsy tissues showed rare ACTH immunoreactivity at the time of initial diagnosis, followed by staining in a greater proportion of cells as the disease progressed, consistent with EAS arising years after the diagnosis of NET. Given the increase in mortality associated with EAS, this unusual case highlights the importance of early detection and raises the possibility that early immunohistochemical stains for ACTH and measurements of ACTH precursors may facilitate the identification of NETs at high risk for EAS.

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 Screening for ACTH-dependent hypercortisolism in patients affected with pituitary incidentaloma

2015 ◽  
Vol 172 (4) ◽  
pp. 363-369 ◽  
Author(s):  
A Toini ◽  
A Dolci ◽  
E Ferrante ◽  
E Verrua ◽  
E Malchiodi ◽  
...  
Keyword(s):  
Early Stage ◽  
Urinary Free Cortisol ◽  
Limited Data ◽  
Subclinical Hypercortisolism ◽  
Chronic Complications ◽  
Systematic Screening ◽  
Pituitary Incidentaloma ◽  
Free Cortisol ◽  
Suppression Test ◽  
Dexamethasone Suppression

ContextPituitary incidentalomas (PIs) are commonly encountered in clinical practice. The management of these asymptomatic pituitary lesions is still controversial. Systematic screening for subclinical or mild ACTH-dependent hypercortisolism (AH) is not presently recommended, due to the limited data available thus far on the epidemiological and clinical relevance of this condition in patients with PIs. As subclinical hypercortisolism (SH) was considered to be associated with chronic complications of overt cortisol excess, such as hypertension, diabetes, and osteoporosis, this disorder should be diagnosed at the early stage.ObjectiveThe objective of this study was to evaluate the prevalence of hypercortisolism in a population of subjects with PIs.Design, subjects, and methodsA total of 68 consecutive patients (48 females and 20 males, aged 18–82 years) without clinically overt hypercortisolism, who were referred for evaluation of PIs between January 2010 and March 2013, were prospectively investigated for AH. Pituitary hypercortisolism was diagnosed in the presence of cortisol >50 nmol/l after 1 mg dexamethasone suppression test, non-suppressed ACTH, and the additional finding of one of the following: urinary free cortisol (UFC) >193 nmol/24 h, and midnight serum and salivary cortisol levels >207 and 2.8 nmol/l respectively.ResultsAmong patients with PIs, we found a 7.3% rate of pituitary hypercortisolism diagnosed with biochemical criteria and a 4.4% rate of histologically confirmed AH.ConclusionsSubclinical or mild hypercortisolism may be more common than generally perceived in patients with PIs.

The Role of Cortisol/ACTH Ratio for Screening of Subclinical Hypercortisolism in Patients with Adrenal Incidentalomas

2017 ◽  
Vol 126 (02) ◽  
pp. 71-76
Author(s):  
Lele Li ◽  
Guoqing Yang ◽  
Jingtao Dou ◽  
Weijun Gu ◽  
Zhaohui Lv ◽  
...  
Keyword(s):  
Area Under The Curve ◽  
Adrenal Incidentaloma ◽  
Serum Cortisol ◽  
Dexamethasone Suppression Test ◽  
Subclinical Hypercortisolism ◽  
Reliable Parameter ◽  
Suppression Test ◽  
Cortisol Levels ◽  
Dexamethasone Suppression

Abstract Introduction The cortisol/ACTH ratio was supposed to be helpful in the screening of subclinical hypercortisolism (SHC) in the published literatures. This study assessed the cortisol/ACTH ratio in patients with adrenal incidentaloma (AI) confirmed to have SHC and investigated its role for screening SCS in patients with AI. Methods This descriptive retrospective study included 183 patients with AIs [45 with SHC and 138 with non-functional adenoma (NFA)]. Cortisol and ACTH levels were measured at 8:00, 16:00, and 0:00, and the cortisol/ACTH ratio was calculated. ROC curve was used to evaluate efficacy of the cortisol/ACTH ratio, explore the best cut-off value and its corresponding sensitivity and specificity. Results The cortisol/ACTH ratios at all time points were significantly higher in the SHC group than the NFA group (P<0.05) and were significantly correlated with serum cortisol levels after the 1-mg dexamethasone suppression test (DST). Area Under the Curve (AUC) of the cortisol/ACTH ratio at 0:00 and midnight serum cortisol levels were 0.893 (0.843–0.943) and 0.831 (0.765–0.806), respectively. A cortisol/ACTH ratio at 0:00 cut-off of 32.18 nM/pM showed a sensitivity of 100% and specificity of 39.1%. The optimal cut-off was 68.83 nM/pM (sensitivity 86.7%, specificity 75.4%). Conclusions Patients with SHC have a higher cortisol/ACTH ratio than those with NFAs. The cortisol/ACTH ratio is significantly correlated with serum cortisol after the 1-mg DST. The diagnostic performance of the cortisol/ACTH ratio at 0:00 is superior to midnight serum cortisol. Therefore, the cortisol/ACTH ratio at 0:00 may be a reliable parameter for SHC screening in patient with AI.

scholarly journals The limited role of midnight salivary cortisol levels in the diagnosis of subclinical hypercortisolism in patients with adrenal incidentaloma

2009 ◽  
Vol 160 (1) ◽  
pp. 87-92 ◽  
Author(s):  
Benedetta Masserini ◽  
Valentina Morelli ◽  
Silvia Bergamaschi ◽  
Federica Ermetici ◽  
Cristina Eller-Vainicher ◽  
...  
Keyword(s):  
Sensitivity And Specificity ◽  
Salivary Cortisol ◽  
Adrenal Incidentaloma ◽  
Urinary Free Cortisol ◽  
Standard Test ◽  
Subclinical Hypercortisolism ◽  
Late Night ◽  
Free Cortisol ◽  
Suppression Test

ObjectiveThe criteria for defining subclinical hypercortisolism (SH) are debated and a real gold standard test or combination of tests is lacking. Recently, late-night salivary cortisol (MSC) has been described as a sensitive and easy-to-perform marker for diagnosing overt hypercortisolism. No data are available on the role of MSC in the diagnosis of SH. The aim of this study was to evaluate the sensitivity and specificity of MSC levels in the diagnosis of SH in patients with adrenal incidentalomas (AI).MethodsIn 103 (females/males, 69/34) patients with AI, MSC levels were studied. One milligram overnight dexamethasone suppression test (DST), urinary-free cortisol (UFC), and ACTH plasma levels were also evaluated. Patients were defined as affected by SH if they showed two of the following criteria: DST>83 nmol/l, ACTH <2.2 pmol/l, and UFC >193 nmol/24 h.ResultsNo difference in MSC levels in patients with SH (3.1±3.1 nmol/l) compared with patients without SH (2.2±2.8 nmol/l) was observed. In patients with SH, MSC levels were significantly correlated with DST (r=0.4,P<0.05). Using the cut-off of 5.1 nmol/l, the sensitivity and specificity of MSC levels for diagnosis of SH is 22.7 and 87.7% respectively.ConclusionIn patients with AI, normal levels of MSC do not exclude SH, whereas high levels may suggest the presence of SH identified by conventional tests. Thus, MSC is not suitable as a screening test, although it may be used in conjunction with other tests as the confirming test in selected patients.

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