Patients With Apparently Nonfunctioning Adrenal Incidentalomas May Be at Increased Cardiovascular Risk Due to Excessive Cortisol Secretion

Androulakis, Ioannis I.; Kaltsas, Gregory; Κόλλιας, Γεώργιος; Markou, Αthina; Gouli, Aggeliki; Thomas, Dimitrios; Alexandraki, Krystallenia Ι.; Papamichael, Christos; Hadjidakis, D.; Piaditis, George

doi:10.1210/jc.2013-4064

Cited by 117 publications

(106 citation statements)

References 42 publications

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“…There was no difference in terms of insulin sensitivity between the two groups of adrenal lesion patients, but subjects with sCS had a significantly higher prevalence of IGT and a higher area under the curve for glucose (19). These data and other studies demonstrate that patients with adrenal incidentaloma, regardless of the functional status, show insulin resistance (20,21,22,23). Moreover, one study found a correlation between adrenal lesion size and insulin resistance (20).…”

Section: Gcs and Glucose Metabolismsupporting

confidence: 54%

“…Therefore, we could turn the question around and ask whether insulin, a known growth factor, might have a potential role in the development and growth of the adrenal lesions (20). On the other hand, patients with non-functioning adrenal lesions could develop insulin resistance because of a subtle alteration of cortisol secretion dynamics not identifiable as autonomous sCS (22).…”

Section: Gcs and Glucose Metabolismmentioning

confidence: 99%

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Metabolic comorbidities in Cushing's syndrome

Ferraú

Korbonits

2015

European Journal of Endocrinology

149

121

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Cushing's syndrome (CS) patients have increased mortality primarily due to cardiovascular events induced by glucocorticoid (GC) excess-related severe metabolic changes. Glucose metabolism abnormalities are common in CS due to increased gluconeogenesis, disruption of insulin signalling with reduced glucose uptake and disposal of glucose and altered insulin secretion, consequent to the combination of GCs effects on liver, muscle, adipose tissue and pancreas. Dyslipidaemia is a frequent feature in CS as a result of GC-induced increased lipolysis, lipid mobilisation, liponeogenesis and adipogenesis. Protein metabolism is severely affected by GC excess via complex direct and indirect stimulation of protein breakdown and inhibition of protein synthesis, which can lead to muscle loss. CS patients show changes in body composition, with fat redistribution resulting in accumulation of central adipose tissue. Metabolic changes, altered adipokine release, GC-induced heart and vasculature abnormalities, hypertension and atherosclerosis contribute to the increased cardiovascular morbidity and mortality. In paediatric CS patients, the interplay between GC and the GH/IGF1 axis affects growth and body composition, while in adults it further contributes to the metabolic derangement. GC excess has a myriad of deleterious effects and here we attempt to summarise the metabolic comorbidities related to CS and their management in the perspective of reducing the cardiovascular risk and mortality overall.

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Section: Gcs and Glucose Metabolismsupporting

confidence: 54%

Section: Gcs and Glucose Metabolismmentioning

confidence: 99%

Metabolic comorbidities in Cushing's syndrome

Ferraú

Korbonits

2015

European Journal of Endocrinology

149

121

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“…In total, 12 studies were included: 7 cross-sectional studies (38,42,43,45,141,142,143) and 5 cohort studies (40,46,144,145,146). In eight studies, a comparison was made between patients with elevated (group 1) or normal (group 2) cortisol levels after a 1 mg dexamethasone test.…”

Section: Assessment Of Autonomous Cortisol Secretion In Relation To Cmentioning

confidence: 99%

Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors

Fassnacht

Arlt

Bancos

et al. 2016

European Journal of Endocrinology

1,335

1,571

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By definition, an adrenal incidentaloma is an asymptomatic adrenal mass detected on imaging not performed for suspected adrenal disease. In most cases, adrenal incidentalomas are nonfunctioning adrenocortical adenomas, but may also represent conditions requiring therapeutic intervention (e.g. adrenocortical carcinoma, pheochromocytoma, hormone-producing adenoma or metastasis). The purpose of this guideline is to provide clinicians with best possible evidence-based recommendations for clinical management of patients with adrenal incidentalomas based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. We predefined four main clinical questions crucial for the management of adrenal incidentaloma patients, addressing these four with systematic literature searches: (A) How to assess risk of malignancy?; (B) How to define and manage low-level autonomous cortisol secretion, formerly called 'subclinical' Cushing's syndrome?; (C) Who should have surgical treatment and how should it be performed?; (D) What follow-up is indicated if the adrenal incidentaloma is not surgically removed? Selected recommendations: (i) At the time of initial detection of an adrenal mass establishing whether the mass is benign or malignant is an important aim to avoid cumbersome and expensive follow-up imaging in those with benign disease. (ii) To exclude cortisol excess, a 1 mg overnight dexamethasone suppression test should be performed (applying a cut-off value of serum cortisol ≤50 nmol/L (1.8 µg/dL)). (iii) For patients without clinical signs of overt Cushing's syndrome but serum cortisol levels post 1 mg dexamethasone >138 nmol/L (>5 µg/dL), we propose the term 'autonomous cortisol secretion'. (iv) All patients with '(possible) autonomous cortisol' secretion should be screened for hypertension and type 2 diabetes mellitus, to ensure these are appropriately treated. (v) Surgical treatment should be considered in an individualized approach in patients with 'autonomous cortisol secretion' who also have comorbidities that are potentially related to cortisol excess. (vi) In principle, the appropriateness of surgical intervention should be guided by the likelihood of malignancy, the presence and degree of hormone excess, age, general health and patient preference. (vii) Surgery is not usually indicated in patients www.eje-online.org European Journal of Endocrinology175:2 G2 Clinical Practice Guideline M Fassnacht and others ESE and ENSAT guideline on adrenal incidentalomawith an asymptomatic, nonfunctioning unilateral adrenal mass and obvious benign features on imaging studies. We provide guidance on which surgical approach should be considered for adrenal masses with radiological findings suspicious of malignancy. Furthermore, we offer recommendations for the follow-up of patients with adrenal incidentaloma who do not undergo adrenal surgery, for those with bilateral incidentalomas, for patients with extra-adrenal malignancy and adrenal masses and for young and elderly patients with adrenal inciden...

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“…Despite the frequency of mild cortisol-secreting adenomas (1,5) and their association with cardiovascular risk and metabolic derangements (3), there remains a lack of consensus regarding formal diagnostic criteria and treatment recommendations for this condition. Furthermore, recent studies showed that patients with "nonfunctional" (post-DST cortisol ≤1.8 µg/dL) adrenal adenomas present with insulin resistance, increased carotid intima medial thickness, and impaired vascular flow, and are at increased risk of developing diabetes (6,7). This raises the question of whether "nonfunctional" adrenal adenomas are truly nonfunctional.…”

Section: Discussionmentioning

confidence: 99%

“…Post-dexamethasone suppression test (DST) serum cortisol values >1.8 µg/dL are considered "possible" autonomous cortisol secretion, and additional testing, including adrenocorticotropic hormone (ACTH), may be indicated to confirm hypercortisolism (5). While cortisol values ≤1.8 µg/dL are thought to exclude autonomous cortisol secretion (5), a growing number of studies have demonstrated increased cardiovascular risk, impaired glucose tolerance, diabetes, and hypertension in patients with "nonfunctional" adrenal adenomas based on this cutoff (6,7). Presented here are two patients with adrenal adenomas whose cases further question the definition of clinically relevant cortisol secretory activity.…”

Section: Introductionmentioning

confidence: 99%

Nonfunctional Adrenal Adenomas: Truth or Myth? Presentation and Treatment of 2 Patients

Moraitis

2018

AACE Clinical Case Reports

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Objective: Autonomous adrenal cortisol secretion is associated with increased frequency of cardiovascular events; however, there is little consensus on what clinical/biochemical criteria should be employed to establish its diagnosis and treatment. Reported here are two cases of autonomous adrenal cortisol secretion that challenge the currently recommended post-dexamethasone suppression test (post-DST) threshold (>1.8 µg/dL) for diagnosing hypercortisolism.Methods: Patient 1, a 64-year-old Caucasian man, presented with hypertension, nephrolithiasis, obesity, and history of a left adrenal tumor (2.1 × 2.9 cm). Baseline morning adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone sulfate (DHEA-S) were normal; 2-day low-dose DST (LDDST) cortisol was 1.2 µg/dL. Patient 2, a 58-year-old Caucasian woman, presented with bilateral adrenal hyperplasia, obesity, depression, and diabetes. Biochemical evaluation showed low-normal morning ACTH (9 pg/mL), low DHEA-S (<15 µg/dL), and 2-day LDDST cortisol of 1.5 µg/dL.Results: Patient 1 underwent left adrenalectomy because of an increase in the size of his tumor. Postoperatively, he developed adrenal insufficiency, which was treated with hydrocortisone. By 3 months postsurgery, he had lost 35 pounds and his blood pressure had improved substantially. Patient 2, based on the equivocal LDDST cortisol results, was treated medically, rather than surgically, with mifepristone (600 mg daily final dose) for 6 months. During treatment, her diabetes and psychological well-being improved, and she lost 18 pounds. Conclusion:The diagnosis of hypercortisolism is evolving. In cases where a link between autonomous adrenal cortisol secretion and related comorbidities is difficult to establish, a therapeutic trial of a glucocorticoid receptor antagonist may be a useful diagnostic/treatment approach. (AACE Clinical Case Rep. 2018;4:e75-e79) Abbreviations: ACTH = adrenocorticotropic hormone; CS = Cushing syndrome; DHEA-S = dehydroepiandrosterone sulfate; DST = dexamethasone suppression test; GR = glucocorticoid receptor; HPA = hypothalamic-pituitary-adrenal; UFC = urine free cortisol

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Patients With Apparently Nonfunctioning Adrenal Incidentalomas May Be at Increased Cardiovascular Risk Due to Excessive Cortisol Secretion

Abstract: Patients with CSAI without hypertension, diabetes, and/or dyslipidemia exhibit adverse metabolic and CVR factors. In addition, NFAIs are apparently associated with increased insulin resistance and endothelial dysfunction that correlate with subtle but not autonomous cortisol excess.

Cited by 117 publications

References 42 publications

Metabolic comorbidities in Cushing's syndrome

Metabolic comorbidities in Cushing's syndrome

Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors

Nonfunctional Adrenal Adenomas: Truth or Myth? Presentation and Treatment of 2 Patients

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