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Keywords:

  • Adrenal incidentaloma;
  • adrenocortical adenoma;
  • subclinical Cushing’s syndrome

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Clinical implications of apparently nonfunctioning adrenal tumours
  5. Consequences of subclinical adrenal hyperfunction
  6. Evolution of a nonfunctioning adrenal mass
  7. Conclusions
  8. Address
  9. References

Eur J Clin Invest 2011; 41 (5): 552–560

Abstract

Background  The term adrenal incidentaloma (AI) indicates an adrenal mass lesion > 1 cm in diameter discovered during testing for conditions unrelated to adrenal disease. The overall prevalence of these lesions ranges between 3% and 10%. Their incidence increases with age, and it is clinically important to identify AI associated with hormonal activity and/or malignant potential.

Design  A detailed Medline search of all English language articles related to AI was carried out, and the clinical implications related to their hormonal activity and malignant potential are discussed.

Results  The subclinical hypercortisolism observed in a significant percentage of patients with AI is associated with some of the detrimental effects of continuous autonomous cortisol secretion, including a higher prevalence of hypertension, dyslipidaemia, impaired glucose tolerance or type 2 diabetes mellitus and an increased risk for osteoporotic fractures. However, it remains to be proven whether treatment to reverse subtle glucocorticoid excess is beneficial. Clinically silent phaeochromocytomas and primary adrenal cancer are conditions associated with significantly high morbidity and mortality and require urgent treatment, while the prevalence and clinical significance of autonomous mineralocorticoid secretion are less clearly defined. Size and radiological features are the main predictors of malignant potential.

Conclusions  Patients harbouring AI should be evaluated for the possibility of malignancy and/or subclinical hypercortisolism which is associated with cardiovascular risk and bone loss. However, in the absence of prospective controlled studies correlating biochemical activity with end-organ complications, the long-term consequences of AI remain uncertain and their management remains largely pragmatic.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Clinical implications of apparently nonfunctioning adrenal tumours
  5. Consequences of subclinical adrenal hyperfunction
  6. Evolution of a nonfunctioning adrenal mass
  7. Conclusions
  8. Address
  9. References

The term adrenal incidentaloma (AI) or a clinically inapparent adrenal mass indicates an adrenal mass lesion > 1 cm in diameter discovered during testing or treatment for conditions unrelated to any suspicion of adrenal disease [1]. This entity was first described 25 years ago and is the result of technological advances and broader availability of imaging technology [2].

Despite the rarity of primary adrenal cancer, adrenal masses are one of the most prevalent human tumours. The prevalence of AI detected at autopsy is < 1% in patients younger than 30 years of age, increasing to 7% in patients 70 years of age or older [3]. Data from the Mayo Clinic indicate a 3·4% prevalence of adrenal masses among 61 054 abdominal computerised tomography (CT) scans performed from 1985 to 1990 [4]. A more recent study, which utilised higher resolution scanners, the reported prevalence of AI on abdominal CT was 4·4% [5].

Adrenal incidentalomas do not constitute a single pathological entity. They can arise from the adrenal cortex or medulla and may or may not manifest autonomous hormone production or growth. After combining studies, the most common aetiologies were as follows: nonfunctioning adenoma 73·9%, subclinical Cushing’s syndrome (CS) 7%, aldosterone-producing adenoma 1·2%, phaeochromocytoma 4·7%, adrenocortical carcinoma (ACC) 4·8% and metastases 2·3% (Table 1).

Table 1.   Prevalence (%) of causes of adrenal incidentalomas
Study (reference)No. of patientsNonfunctioning adenoma (%)Subclinical Cushing’s syndrome (%)Aldosterone-producing adenoma (%)Pheochromo-cytoma (%)Adrenocortical carcinoma (%)Metastases (%)
Herrera et al. 1991 [4]34295·90·601·51·170·3
Reincke et al. 1992 [6] 6885·311·81·51·500
Bencsik et al. 1995 [7]6350·820·6001·5911·1
Linos et al. 1996 [8]5784·28·807·03·513·5
Kasperlik-Zaluska et al. 1997 [9]20870·22·909·18·659·1
Terzolo et al. 1997 [10]21058·614·30·54·87·140·9
Bastounis et al. 1997 [11]8661·63·502·331·162·3
Proye et al. 1998 [12]10369·904·814·64·853·9
Murai et al. 1999 [13]5972·91·71·718·65·080
Rossi et al. 2000 [14]6558·518·507·73·083·1
Favia et al. 2000 [15]15876·65·13·82·59·491·9
Mantero et al. 2000 [16]100471·39·21·64·24·681·2
Bulow & Ahren 2002 [17]38184·21·00·53·92·62·1
Barzon et al. 2002 [18]28464·811·32·15·98·802·8
Total30882283 (73·9%)216 (7%)38 (1·2%)146 (4·7%)148 (4·8%)70 (2·3%)

A major determinant of the prevalence of AI in both autopsy and clinical series is age. The prevalence of incidentalomas detected at autopsy peaks between the 5th and 7th decades of life [19]; consequently, as the population ages, the management of AI is becoming an increasingly important aspect of health care. Arbitrarily, the definition of incidentaloma rules out patients undergoing imaging procedures for cancer staging and work-up; in addition, there should be no clinical symptoms or signs of adrenal disease at the time of diagnosis. In retrospect, however, patients were often found to have had signs or symptoms of hormone oversecretion, albeit in mild forms, while arterial hypertension and obesity are significantly more prevalent in patients with AI [20].

Following the demonstration of an adrenal mass, the differential diagnosis should consider adrenal CS, phaeochromocytoma, primary aldosteronism, primary and metastatic malignancy, myelolipoma and nonhypersecretory cortical adenoma [1,19,21–23]. Differentiating between malignant and benign masses is essential because metastases to the adrenal glands are common. Adenomas, comprising the vast majority of incidental asymptomatic adrenal masses, are benign, and there is no evidence that they progress into malignant lesions [24]. Adrenal cortical carcinoma is rare, but remains of great clinical concern because of its high mortality rate. The diagnostic challenge is to recognise and treat the percentage of AI that pose a significant health risk, because of either hormonal activity or risk of malignancy, and distinguish them from those that are neither hyperfunctioning nor malignant.

In the present review, a detailed Medline search of articles related to AI was carried out, and the clinical implications related to their hormonal activity and malignant potential are discussed.

Clinical implications of apparently nonfunctioning adrenal tumours

  1. Top of page
  2. Abstract
  3. Introduction
  4. Clinical implications of apparently nonfunctioning adrenal tumours
  5. Consequences of subclinical adrenal hyperfunction
  6. Evolution of a nonfunctioning adrenal mass
  7. Conclusions
  8. Address
  9. References

Patients with clinically inactive adrenal adenomas as a group exhibit insulin resistance (IR) and a variety of metabolic disturbances and manifestations of the metabolic syndrome [3,16,22,25,26]. In a multi-institutional study of 1004 patients with AI, the prevalence of arterial hypertension, diabetes mellitus type 2 (DM type 2) or obesity were 41%, 10% and 28%, respectively [16]. Furthermore, a remarkably high prevalence of impaired glucose tolerance (IGT), or previously unknown DM type 2, increased visceral fat mass, and hyperinsulinaemia has been found among patients with nonfunctioning adrenal tumours [27,28]. The degree of metabolic and body fat alterations is reported to be intermediate between that of controls and patients with overt CS [28]. The limited available data suggest that most patients with AI die of causes not strictly related to the adrenal mass itself but mostly from cardiovascular events, although it still not known whether the mortality rate is higher than the general population [29,30].

This insulin-resistant state is probably associated with subtle cortisol autonomy leading to an increased incidence of several cardiovascular risk factors. Patients with AI exhibit elevated levels of D-dimers [31], interleukin-6 (IL-6), adiponectin, resistin, tumour necrosis factor (TNF)-alpha and monocyte chemoattractant protein 1 (MCP-1) [32]. Such patients also show an impairment of cardiac morphology and function as reflected by the impairment of echocardiographic indices of left ventricular hypertrophy and diastolic dysfunction [33]. Furthermore, they present other subtle indices of atherosclerosis, such as increased carotid intima media thickness, which is also correlated with morning cortisol levels [34]. Finally, even slight glucocorticoid excess exerts inhibitory effects on TSH secretion, suggesting the presence of mild central hypothyroidism in patients with AI [35].

Consequences of subclinical adrenal hyperfunction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Clinical implications of apparently nonfunctioning adrenal tumours
  5. Consequences of subclinical adrenal hyperfunction
  6. Evolution of a nonfunctioning adrenal mass
  7. Conclusions
  8. Address
  9. References

Subclinical Cushing’s syndrome (CS)

Although the majority of AI are nonhypersecretory adenomas, many patients present isolated or multiple mild hypothalamic-pituitary-adrenal (HPA) abnormalities, such as elevated or high normal urinary-free cortisol excretion, impaired cortisol rhythm, partial cortisol suppression to dexamethasone administration, low plasma adrenocorticotropic hormone (ACTH) levels and/or poor responses to corticotropin-releasing hormone [14,26,36–38]. Adrenal insufficiency following surgical excision of presumed nonsecretory adrenal adenomas has been described in 18–20% of cases, suggesting the presence of mild hypercortisolism that is called subclinical CS (SCS) [19]. This term is used to define a condition characterised by alterations of HPA function in keeping with a subtle cortisol hypersecretion in the absence of signs and/or symptoms specific of overt hypercortisolism [20]. Rarely, cortisol secretion can be under the control of one or more aberrant hormone receptors in patients with unilateral adenomas or incidental bilateral ACTH-independent macronodular hyperplasia [39].

Subclinical CS is the most frequent hormonal abnormality detected in patients with AI, with a prevalence that ranges from 5% to 47% in various studies [3,14,20,23,26,29,36,40,41]. This wide variation is mainly attributed to the different work-up protocols and variable criteria used to define subclinical cortisol excess, as well as in different inclusion criteria and size of reporting series. However, it is difficult to characterise this endocrine disorder as there is a continuum from normality to autonomy, and the degree of cortisol excess may be only slightly higher than the physiological daily cortisol output [3,42]. Following the suggestion that even subclinical hormone overproduction by AI may be associated with a greater morbidity if left untreated, the threshold for treating SCS has been lowered in the last decade [1,3,43].

Because many patients with clinically nonfunctioning incidentalomas are exposed to a chronic, even if only minimal to mild, cortisol excess, it is biologically plausible to anticipate that they should suffer, at least to some extent, from the classic long-term consequences of overt CS [24,44]. Although AI patients with SCS lack many of the usual stigmata of overt CS, they may exhibit one or more of the effects of continuous autonomous cortisol secretion [45]. Indeed, patients with SCS are more likely to have hypertension, dyslipidaemia, IGT or type 2 DM and evidence of atherosclerosis [46]. Furthermore, they exhibit increased waist-to-hip ratio, increased indices of IR and significant changes in carotid intimal-medial thickness [37]. These data are in agreement with the view that SCS may be associated with the clinical phenotype of the IR syndrome as the subtle autonomous cortisol secretion may cause IR in otherwise normoglycaemic and nonobese subjects [25]. An alternative hypothesis is that AI may be a consequence rather than cause of the metabolic syndrome [47]; however, a causal link between SCS and IR remains the most plausible explanation [48]. In SCS, the cortisol secretion is probably a continuum between normal and clear-cut cortisol excess and may be intermittent. Therefore, this subtle cortisol hypersecretion may be not reliably revealed by the commonly employed biochemical markers [3,38,49].

Many of the features encountered in patients with AI, such as central fat deposition, hypertension and low high-density lipoprotein (HDL) levels, are important predisposing factors for the development of cardiovascular disease putting subjects with AI at greater risk than the general population. However, studies specifically designed to investigate the possible benefits from treatment of SCS are partially conflicting, although all suggested an improvement in hypertension [14,44,50–52]. Although some authors have described an improvement of all features of the metabolic syndrome in patients with SCS following the removal of the adrenal mass [14,36,52,53], others have not [44,50,51]. These discrepancies may be because of the different criteria adopted to define SCS, insufficient sample size and differences in the duration of follow-up and timing of postoperative evaluation.

Obesity in patients with SCS.  Hypercortisolism is characterised by a redistribution of adipose tissue from peripheral to central sites of the body, mainly in the truncal region and visceral depots [54]. Central abdominal obesity determined by waist-to-hip ratio and dual-energy x-ray absorptiometry is more frequent in patients with SCS [14,28]. Surgical treatment of subclinical hypercortisolism in patients with AI is associated with a significantly higher probability of improving body weight [55].

Diabetes mellitus type 2 and glucose metabolism in patients with SCS.  Several observations have suggested that DM type 2 in patients with SCS may be more frequent than previously appreciated [56,57]. In a controlled study, the proportion of SCS in patients with DM type 2 was estimated to be higher than controls [58]; however, a subsequent study failed to support the validity of screening diabetic patients without clinical features of CS [59]. The presence of SCS in diabetic patients is associated with poor metabolic control [14,25,37,58]. However, surgical treatment of SCS in patients with AI has yielded conflicting results. In some series, adrenalectomy did not seem to improve glucose metabolism [44,51], whereas in one study it was associated with a significant improvement in fasting glucose levels in 52·5% of patients [52].

Hypertension in patients with SCS.  Blood pressure values are higher in patients with AI compared to healthy matched individuals [28]. Furthermore, approximately 50% of patients with AI are hypertensive [28]. Surgical excision of AI in patients with SCS is associated with normalisation of blood pressure and/or a significantly higher probability of improving blood pressure levels [55].

Dyslipidaemia in patients with SCS.  HDL cholesterol levels are lower, and triglyceride levels are higher, in AI patients with SCS compared to controls [28]. However, the effects of surgical treatment on lipid profile are conflicting as in one study adrenalectomy did not show any effect [44], whereas in others it led to restoration of lipid levels to normal in 37·5% of patients [52].

Bone metabolism in patients with SCS.  Overt endogenous glucocorticoid excess is a well-recognised cause of bone loss and osteoporotic fractures [60]. Cortisol excess inhibits bone formation, increases bone resorption, impairs calcium absorption from the gut and affects the secretion of several hormones (particularly gonadotrophins and GH), cytokines and growth factors influencing bone metabolism [60]. Subclinical hypercortisolism has been shown to be associated with increased bone resorption, bone loss and a high prevalence of vertebral fractures [45,61,62]. The degree of clinical consequences of SCS on bone metabolism varies with the extent of hormone overproduction [63]. In a recent study, patients with AI and SCS exhibited reduced bone density, architectural deterioration of trabecular bone and an increased prevalence of vertebral fractures [45]. In a further study, it was shown that subclinical hypercortisolism is a common and underrated finding in patients with established osteoporosis [60]. Although no improvement in bone parameters was documented in patients with SCS after adrenalectomy [52,64], antiresorptive treatment resulted in significant increase in lumbar BMD and bone turnover markers [65]. Further longitudinal studies of adequate statistical power are needed to estimate the risk of osteoporotic fractures and their attendant impact on outcome and quality of life.

Subclinical hyperaldosteronism

Primary aldosteronism is probably more common nowadays than previously reported [66]. The prevalence of mineralocorticoid-secreting masses in hypertensive patients with AI has been estimated to range between 1·6% and 5% [23,67] More recent series that have employed more sophisticated diagnostic procedures have suggested that in patients with AI subclinical autonomous aldosterone secretion is much more common than previously appreciated and that it correlates with diastolic blood pressure [40]. However, further research in this area is needed to confirm these findings and correlate them with relevant clinical end-points.

‘Silent’ phaeochromocytoma

Phaeochromocytoma, though usually histologically mostly benign, is a potential lethal disorder with an unpredictable course [68]. Approximately 0·01–0·1% of all hypertensive patients have been shown to harbour a pheochromocytoma but the majority lack the classic clinical triad of phaeochromocytoma (headache, palpitations and diaphoresis), and the diagnosis is easily overlooked or delayed [67]. Furthermore, hypertension is constant in only about half of the patients, paroxysmal in a third and absent in about 20% [69]. The mean interval between initial presentation and diagnosis is estimated to be 3·5 years with a reported delay as long as 30 years in extreme cases [70]. Imaging findings consistent with phaeochromocytoma include increased attenuation on unenhanced CT, prominent vascularity of the mass and delayed washout of intravenous contrast medium [69] (Fig. 1). CT can identify phaeochromocytomas above 1 cm in diameter with a 77–98% and 29–92% sensitivity and specificity, respectively [71]. CT scans of suboptimal technology confer limited diagnostic accuracy and make biochemical evaluation mandatory. Phaeochromocytmas exhibit a high signal intensity on T2-weighted magnetic resonance imaging (MRI), and MRI T2-weighted imaging has a sensitivity and specificity in identifying phaeochromocytoma of approximately 92% and 88%, respectively [72].

image

Figure 1.  Computerised tomography of a benign adrenocortical adenoma of the left adrenal (arrow).

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Clinically silent phaeochromocytoma is not rare, and its prevalence in patients with AI has been estimated between 1·5% and 13% [23]. In the larger series of AI, phaeochromocytoma was the second most prevalent form of hyperfunctioning tumour occurring in 4·2% of all masses [16]. Silent phaeochromocytomas can carry a significant morbidity and mortality if not diagnosed early. This is highly relevant as in autopsy series phaeochromocytoma was found in 0·13% of cases, and the tumour had not been suspected in 75% of the patients while alive, although it contributed to their death in approximately 55% of cases [68]. About half of the patients with AI that proved to harbour phaeochromocytomas were normotensive, while the others had mild-to-moderate hypertension [19].

Adrenocortical carcinoma

The most feared diagnostic possibility for AI is ACC, which has a mean survival of approximately 18 months and a 5-year overall survival of around 16% [43]. ACC is rare, with an incidence ranging from 0·6 to 2 cases per million population per year [43,73]. Although ACC can develop at any age, there is a bimodal age distribution, with disease peaks before the age of 5 years and in the 4th to 5th decade of life [74]. Adrenocortical carcinomas are increasingly detected as incidentalomas during abdominal imaging [75]. The prevalence of primary adrenal carcinoma in clinically inapparent adrenal masses correlates with the size of the mass [43]. Adrenal cortical carcinoma accounts for 2% of tumours up to 4 cm in size, 6% of tumours between 4·1 cm and 6 cm and 25% of tumours that are larger than 6 cm; the larger the diameter of the mass, the greater the risk of it being malignant [23]. These tumours can be either functioning or nonfunctioning, the former accounting for approximately 60%, with CS either alone or in association with virilisation is the most frequent presentation [75]. In a series of 1004 AI, the relative rate of malignancy was 4·6% [16].

Imaging features on adrenal CT are used to distinguish adenomas from malignant lesions. Adrenal adenomas are usually small, well-defined homogeneous lesions with clear margins and high lipid content, whereas malignant lesions are larger, have an irregular border, vague contour, invade into surrounding structures and exhibit high signal intensity [21]. Signal intensity lower than 10 Hounsfield units is highly indicative of a benign adrenal lesion [76] (Fig. 2). Benign adenomas are also characterised by rapid absolute and relative washout of intravenous contrast; a relative washout value of more than 40% has a sensitivity and specificity of 96% and 100%, respectively, in identifying adenomas [77,78]. The combination of unenhanced CT intensity and washout values can distinguish adenomas from other adrenal tumours with 98% sensitivity and 92% specificity [77,79]. The accuracy of MRI in the differentiation between benign and malignant tumours is comparable to that of CT scanning, particularly using in-and out-of-phase imaging [80]. Normal adrenal glands have T1 and T2 signal intensity equal or slightly lower than that of the normal liver, whereas malignant masses are hypointense on T1 and hyperintense on T2-weighted images and exhibit strong enhancement after contrast injection and delayed washout [81]. Most ACCs accumulate and retain [18F]-fluorodeoxyglucose (FDG) and thus can be visualised by FDG positron emission tomography (FDG PET) [82]. In a recent prospective multicenter study that included 77 patients who underwent surgery, the degree of preoperative FDG PET uptake predicted with high precision the pathological findings [83]. Using a cut-off value above 1·45 for adrenal to liver maximum standardised uptake value (maxSUV) ratio, the sensitivity and specificity to distinguish adrenocortical adenomas from ACCs were 100% and 88%, respectively [83]. Although the imaging phenotype does not predict hormonal function, it does not necessarily predict the underlying pathology either, and therefore, surgical resection should be considered for patients who have AI with a suspicious imaging phenotype.

image

Figure 2.  T2-weighted image with fat saturation in a phaeochromocytoma of the right adrenal gland (arrow).

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Evolution of a nonfunctioning adrenal mass

  1. Top of page
  2. Abstract
  3. Introduction
  4. Clinical implications of apparently nonfunctioning adrenal tumours
  5. Consequences of subclinical adrenal hyperfunction
  6. Evolution of a nonfunctioning adrenal mass
  7. Conclusions
  8. Address
  9. References

Follow-up of patients with nonfunctioning adrenal masses suggests that although 5–25% may increase in size by at least 1 cm and 3–4% may decrease, the majority remain stable [9,30,84,85]. The threshold for clinically significant increases in size is unknown, particularly because the reproducibility of size determination by imaging procedures is poorly defined [81].

Evolution of silent hypercortisolism to overt CS occurs rarely, while the appearance of silent biochemical alterations is found in 0–11% in different studies [41]. Masses of 3 cm in size or greater are more likely to develop silent hyperfunction than smaller tumours, and this risk seems to plateau 3–4 years after the diagnosis [84]. In some series, no case of evolution from subclinical to overt CS was observed, even if several endocrine modifications occurred during follow-up [85,86]. In selected cases, spontaneous regression of the alterations of the HPA axis may be observed, and this finding suggests that cortisol hypersecretion may have a cyclical pattern [86]. In a prospective study of 229 patients with AI that were followed for up to 108 months (median period of 25, range from 3 to 108 months), two patients were diagnosed with CS within the first 48 months, one patient was found to have a phaeochromocytoma after the 4th year of observation, while none developed primary hyperaldosteronism or malignancy [87].

The presence of intermittent subclinical autonomous cortisol hypersecretion in a significant percentage of patients supports the wide range of variability in adrenal adenomas, from nonfunctioning to autonomous cortisol secretion [88]. Mass enlargement and the presence or occurrence over time of subclinical endocrine activity are frequent and not correlated, may appear at any time, are not associated with any basal clinical, biochemical or morphological predictors, and are not necessarily indicative of malignant transformation or of progression to overt disease [86]. However, a recent review of all published series of AI suggested that the prevalence of malignant and functional lesions in AI is likely to have been overestimated as the possibility of development of functionality or malignancy during follow-up was ≤ 1% and 0·2%, respectively [89]. Furthermore, exposure to ionising radiation during the recommended CT scan follow-up confers a one in 430–2170 chance of causing fatal cancer that is similar to the chance of developing adrenal malignancy during a 3-year follow-up period of an AI [89]. Until additional information from large prospective studies is available, it is reasonable to repeat imaging studies 6 months after the diagnosis and then annually and the hormonal screening annually for 4 years, as suggested by the National Institutes of Health (NIH) state-of-the-science statement [3]. However, with smaller nonfunctioning masses which show no sinister imaging characteristics, it is probable that follow-up beyond 6–12 months is unnecessary.

Conclusions

  1. Top of page
  2. Abstract
  3. Introduction
  4. Clinical implications of apparently nonfunctioning adrenal tumours
  5. Consequences of subclinical adrenal hyperfunction
  6. Evolution of a nonfunctioning adrenal mass
  7. Conclusions
  8. Address
  9. References

Adrenal incidentalomas that are found to be adrenal carcinomas, metastatic deposits or phaeochromocytomas are life-threatening and need immediate management. However, it is unclear whether nonsecreting or subclinically secreting adrenocortical adenomas pose potential harm to patient health, particularly as information from randomised trials to guide their optimal management are lacking (Fig. 3). Even though SCS, which is the most common functioning state of an AI, may lead to IR, it is presently unknown whether overall mortality is increased in such patients. The reported high prevalence of autonomous aldosterone secretion in hypertensive patients with AI is an interesting suggestion that requires further study. Prospective adequately powered studies to address disease-specific or all-cause mortality are needed to evaluate the potential cardiovascular morbidity linked with AI, substantiate whether adrenalectomy is beneficial and select patients that are the best candidates for this approach.

image

Figure 3.  Adrenal incidentalomas: overview of potential clinical implications.

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Address

  1. Top of page
  2. Abstract
  3. Introduction
  4. Clinical implications of apparently nonfunctioning adrenal tumours
  5. Consequences of subclinical adrenal hyperfunction
  6. Evolution of a nonfunctioning adrenal mass
  7. Conclusions
  8. Address
  9. References

Department of Pathophysiology, National University of Athens, Mikras Asias 75, 11527, Athens, Greece (I. I. Androulakis, G. Kaltsas); Department of Endocrinology and Diabetes, General Hospital of Athens ‘G. Genimatas’, Leoforos Mesogion, 154, Athens, Greece (G. Piaditis); Department of Endocrinology, St Bartholomew’s Hospital, Barts and the London School of Medicine, West Smithfield, EC1A 7BE, London, UK (A. B. Grossman).

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Clinical implications of apparently nonfunctioning adrenal tumours
  5. Consequences of subclinical adrenal hyperfunction
  6. Evolution of a nonfunctioning adrenal mass
  7. Conclusions
  8. Address
  9. References