Introduction Adrenal incidentalomas have become a common clinical dilemma with the increasing use and resolution of cross sectional imaging modalities.
Objectives This retrospective observational study examined the management of adrenal incidentalomas in district general hospitals in Northumbria and adherence to current guidelines.
Materials and methods We searched 4028 abdominal CT scans performed in Northumbria between 1 January and 31 December 2010. All patients with an incidental adrenal lesion were identified and their clinical records reviewed.
Results 75 patients with adrenal incidentalomas were identified. Of these, only 13 (17%) were referred for specialist review with a further two patients undergoing additional evaluation by the primary medical team; 80% received no biochemical investigation or follow-up. Comorbidity may have affected the decision in a proportion, but 36 of 62 patients (58%) had no comorbidities precluding additional evaluation. In contrast, all patients reviewed by an endocrine specialist were appropriately investigated and managed, the majority conservatively, with three requiring adrenalectomy for phaeochromocytoma or cortisol secreting adenomas. In the patients with an incidentaloma, comorbidities which may be attributable to autonomous adrenal cortisol or aldosterone release were higher than regional averages, suggesting possible undiagnosed functional tumours.
Conclusions The management of adrenal incidentalomas in British district general hospitals in Northumbria shows poor adherence to guidelines. Adherence was significantly better in those patients managed by an endocrine specialist. We suggest a pathway for the management and referral process.
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Adrenal incidentaloma is defined as an adrenal tumour discovered by chance during the investigation of an unrelated condition, such as abdominal pain or an acute respiratory illness1 (figures 1 and 2). This has become a common clinical dilemma due to an increase in the use and resolution of imaging modalities, such as CT, MRI and ultrasound. The incidence increases with age, with autopsy studies suggesting an overall 6% prevalence of adrenal mass lesions.2 Frequency of detection on CT scanning is quoted as 1–4%.3 ,4 ,7 The majority of these lesions are benign, non-functional adrenal adenomas,5 but other potential diagnoses include functional adenoma of the adrenal cortex (secreting aldosterone, cortisol or androgens), phaeochromocytoma, adrenocortical carcinoma, metastases, myelolipoma, ganglioneuroma, lymphoma and other rare entities (see table 1).
Optimal management of the adrenal incidentaloma has been the subject of debate for some time.6 Numerous guidelines exist, the most recent being those published by the American Association of Clinical Endocrinologists and American Association of Endocrine Surgeons (AACE) in 2009 (box 1).7 British surgical guidelines were published by the British Association of Endocrine and Thyroid Surgeons in 2003.
Summary of AACE guideline features used in this study7
All patients with adrenal incidentaloma should undergo evaluation clinically, biochemically and radiologically for symptoms and signs of hypercortisolism, hyperaldosteronism (if hypertensive), the presence of a phaeochromocytoma or a malignant tumour
Suggested biochemical testing:
a 1 mg dexamethasone suppression test (hypercortisolism)
plasma free metanephrines and normetanephrines, or 24 h urinary metanephrines and catecholamines (phaeochromocytoma)
plasma aldosterone to renin ratio (hyperaldosteronism)
All patients with a phaeochromocytoma or adenoma producing excess cortisol or aldosterone should undergo adrenalectomy
Any adrenal mass with concerning radiological characteristics and most ≥4 cm should be resected because of the risk of adrenal malignancy
Any suspected adrenocortical carcinoma should undergo open resection
During evaluation of an adrenal incidentaloma, the most important distinction to make is between potentially malignant or functional masses, which may require urgent treatment, and those that are non-functional, benign and can be safely observed. Failure to differentiate between these may lead to significant patient morbidity and mortality.8 ,9 Despite this, adrenal incidentalomas are often overlooked, and management is generally poor, even in large tertiary hospitals where specialist advice is readily available.10–12
This study aims to examine the adequacy of management of adrenal incidentalomas in British district general hospitals, on which there is very little previously published literature. Our objectives were to assess the incidence and epidemiology of adrenal incidentalomas outside of a tertiary hospital setting, referral practices, compliance to management guideline recommendations (by both non-specialist and specialist teams) and to examine patient comorbidities suggestive of subclinical excess cortisol secretion or hyperaldosteronism as an indication of potentially missed functional tumours.
Materials and methods
Northumbria Healthcare NHS Foundation Trust encompasses the northernmost region of England, serving a population of approximately 550 000.
Northumbria Healthcare NHS Foundation Trust13
Provides healthcare to over half a million people via:
3 district general hospitals
6 community hospitals
health services in the community
Serves one of the geographically largest areas of any NHS trust in the UK
Provides healthcare to a population which, compared with the national average, has:
Lower rates of deprivation
Higher rates of adult obesity
Higher rates of hospital admission for alcohol related illnesses
Lower female life expectancy
We surveyed the outcome of all adrenal incidentalomas identified within the trust over a 1 year period, commencing 1 January 2010. Patients with a previously identified adrenal lesion were excluded.
Using clinical codes, we searched reports from all abdominal CT scans performed during this period for the following terms: adrenal mass, lesion, swelling, cyst, tumour, nodule, incidentaloma or adenoma, enlarged or bulky adrenals. Case notes were examined for all patients with positive findings and further details, including patient demographics, indication for imaging and incidentaloma characteristics, were recorded. Data regarding investigations performed (including further imaging, blood, salivary and/or urine analysis of biochemical functionality), referral to a specialist endocrine team and treatment received (surgical, medical and/or surveillance) were collated for each patient and compared with the AACE guidelines for the management of adrenal incidentalomas (box 1).7 Where management deviated from guidelines, we examined case notes for justification.
Comorbidities that may be attributable to autonomous steroid or aldosterone overproduction, including hypertension (>140/90 mm Hg), obesity (body mass index >30 kg/m2), osteoporosis, as defined on dual energy X-ray absorptiometry scanning, and diabetes mellitus (DM) type II were established from review of the case notes and compared with regional averages published by the network of public health observatories in the UK.14
Basic statistical analysis was used to calculate incidence and mean epidemiological data. The proportion of patients who underwent recommended investigations as per the AACE guidelines was calculated for both patients referred for endocrine subspecialty review and those managed by non-specialist teams.
Incidence and epidemiology
Between 1 January and 31 December 2010, 75 patients with 108 (33 patients had bilateral adenomas) new adrenal incidentalomas were identified from 4028 CT scans, giving a CT incidence of 1.86%. There was no gender difference and mean age at discovery was 68 years (range 41–93 years). Thirty-five (46.7%) patients with adrenal incidentalomas had a current diagnosis of malignancy in another organ, with another five (6.7%) having a previous history of malignancy. Most CT requests (59%) were for outpatients with the remainder being inpatient requests. Indications for scan requests and imaging characteristics are detailed in tables 2 and 3.
There was no documentation acknowledging the CT finding, any further diagnostic evaluation or referral in the majority (56%) of patients with adrenal incidentalomas. Only 13 (17%) patients with adrenal incidentalomas were reviewed by a specialist endocrinologist or endocrine surgeon (figure 3). Two patients underwent biochemical testing without specialist referral and eight had further imaging arranged by the primary medical team. Of the 62 patients not referred, 26 (42%) were ultimately diagnosed with inoperable metastatic cancer. The remaining 36 patients (58%) had no comorbidities evident on review of the case notes that precluded investigation of their adrenal incidentaloma.
Effect of endocrine specialist involvement
The majority of patients reviewed by an endocrine specialist were managed non-operatively (figure 3). All patients, excluding those in whom results would not have changed management due to underlying comorbidities, were investigated and treated appropriately as per AACE guideline recommendations. Three patients underwent adrenalectomy, with histology confirming a phaeochromocytoma in one and cortisol secreting adenomas in two.
Comorbidities associated with autonomous steroid overproduction and hyperaldosteronism
Almost half of the patients had two or more comorbidities associated with autonomous steroid overproduction (hypertension, obesity, osteoporosis, type II DM) or hyperaldosteronism (hypertension and type II DM), and the incidence rates of hypertension and type II DM were higher than regional averages (figure 4). Accurate regional data of the prevalence of osteoporosis were unavailable.
This study examined the adequacy of management of adrenal incidentalomas in British district general hospitals. Our data suggest that the incidence and epidemiology of adrenal incidentalomas outside of a tertiary hospital setting are in keeping with other centres, with a CT incidence of 1.8%.4 ,6 The vast majority of patients were not referred for endocrine specialist review, and in these patients adherence to management guideline recommendations was poor. In contrast, when specialist involvement was apparent, adherence was excellent. Although this study shows poor adherence to guideline recommendations in district general hospitals, results from tertiary centres suggest care may be no better, although no comparative studies exist.10–12 An increased rate of comorbidities in our patients suggests the potential for missed functional tumours.
Due to this being a purely observational retrospective study, the clinical implications of lack of guideline adherence have not been evaluated and can only be inferred. The majority of lesions were not formally recorded in case notes and did not receive recommended diagnostic evaluation or assessment for the need for surgery. This may suggest an opportunity to reduce morbidity and mortality for patients with adrenal incidentalomas in the district general hospital setting.
Of greatest concern in our study is the potential for missed malignancy. Over half of the patients who did not undergo further investigation or subspecialist review had no obvious precluding comorbidity. Five patients had incidentaloma features on CT suspicious for malignancy. Suspicious CT features include size larger than 4 cm, a high attenuation lesion (Hounsfield units ≥10 on a non-enhanced scan), increased vascularity, heterogenous texture and delayed contrast washout at 10–15 min.15 Unless the lesion is obviously a myelolipoma on imaging, common practice is surgical resection of all masses larger than 4 cm as well as any functional lesions or those with malignant or indeterminate features.
In addition, our study may have included patients with undiagnosed benign functional adrenal tumours, as 80% of patients did not undergo biochemical evaluation. If left untreated, these can also lead to significant morbidity and mortality. An undiagnosed phaechromocytoma in a patient undergoing surgery or procedural intervention is associated with significant perioperative risk, including a mortality rate of up to 80%.9 Undiagnosed hyperaldosteronism can result in uncontrolled hypertension and electrolyte imbalance, with subsequent increased risk of cerebrovascular, cardiovascular and renal disease. Likewise, autonomous corticosteroid overproduction in patients without overt features of Cushing's syndrome (so-called subclinical Cushing's syndrome) with increased susceptibility to infection, impaired wound healing and anastomotic failure is important to recognise. In addition, in those with hypercortisolism that do undergo surgery, steroid replacement should be administered in the perioperative and postoperative periods to avoid the risk of Addisonian crisis. It is notable that the incidence of comorbidities associated with autonomous steroid overproduction or hyperaldosteronism in this group of patients was particularly high compared with regional averages. This has been observed in other studies16 and may suggest that a proportion of these lesions were functional. It is recognised that, as the mean age of patients in this study was 68 years and both type II DM and hypertension are strongly age related, these comparisons may overestimate the true increase in prevalence of these comorbidities in patients with adrenal incidentaloma compared with the regional population.
The indication for CT scan in a significant proportion of patients in this study was staging or investigation of an unrelated primary malignancy. The incidental finding of an adrenal mass on staging of a patient with operable malignancy in other organs creates a dilemma, as endocrinological workup is needed which may be difficult to achieve within the time constraints for performing surgical resection of the primary malignancy. In this situation, development of a fast track pathway to endocrine evaluation would be valuable.
Referral to an endocrinologist or endocrine surgeon for further management occurred in less than one-fifth of patients in our study. For those patients who were seen by a specialist, adherence to guidelines was excellent. Investigations in the form of imaging and biochemical testing as well as non-operative surveillance were in accordance with management in other centres.17 Our operative rate of 25% was higher than expected from the literature3 ,7 and may reflect referral bias.
This study has several limitations. It was retrospective and observational. Study numbers were small. The true incidence of adrenal incidentalomas in Northumbria Trust may have been underestimated in this study as only reports from CT scans were interrogated which ignores other imaging modalities, such as ultrasound and MRI. Lack of patient follow-up in our purely observational study does not allow assessment of the clinical significance of our findings.
Ideally we would have compared our management with locoregional or UK national guidelines. We chose to use the AACE guidelines as the accepted approach to the management of adrenal incidentaloma has evolved since the publication of national guidelines by the British Association of Endocrine and Thyroid Surgeons (BAETS) in 2003.18
Further research investigating guideline awareness and reasons for poor adherence would be helpful to identify areas on which to focus to improve management of patients with adrenal incidentalomas in district general hospitals. As a result of this study, local clinical guidelines have been drawn up in Northumbria Trust in the expectation that these lesions will be managed more appropriately in our patients.
Adrenal incidentalomas in British district general hospitals in Northumberland are a common clinical dilemma. This study shows that management guidelines are not being implemented and as a consequence the majority of affected patients are not receiving appropriate investigation. Referral to an endocrinologist or endocrine surgeon is an important first step to ensure appropriate management, which will be non-operative in most. High rates of comorbidities associated with excess cortisol or aldosterone secretion may suggest missed functional tumours. Awareness of appropriate management guidelines and referral pathways for adrenal incidentalomas needs to be raised among general clinicians. In our trust, a pathway has been developed which we hope will improve patient care (figure 5).
Management of adrenal incidentalomas in district general hospitals in Northumberland shows poor compliance with guideline recommendations.
Referral to an endocrine specialist significantly increases the likelihood of appropriate investigation and treatment.
Adrenalectomy was required in 25% of patients referred to an endocrine specialist.
Current research questions
Why are so many patients with adrenal incidentalomas not receiving appropriate workup or management?
How can we improve management of adrenal incidentalomas?
What is the degree of morbidity/mortality associated with inappropriate management of adrenal incidentalomas?
We would like to acknowledge the assistance of Dr Nicholas Lewis-Barned, consultant endocrinologist Northumbria Healthcare NHS trust, particularly with regards to figure 5.
Contributors All authors contributed significantly to the paper, and have read and consented to its submission.
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.
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