An Audit on The Management of Incidentalomas in a District General Hospital in the UK

Indrajit Talapatra (MRCP) and Ian O’Connell (FRCP)
Royal albert Edward Infirmary, Wigan, UK

Aim:

To find out if the patients who were seen at the Endocrine out-patients between 15th October 2016 and 15th March 2017 with Adrenal Incidentalomas were managed according to the European Guidelines

Methods:

A search was made on the EPR (Electronic patient Records) under “Radiology Report Search” with the names of the “Doctors” (Endocrine consultants) and with the criteria of “Adrenal Scan” and “Adrenal Adenomas” in the box of “Favourite Search” and the patients seen between the middle of October 2016 and the middle of March 2017 were studied

Guidelines:

The European Guidelines (2016) were considered for the purpose of the audit (1)

Discussion:

An adrenal Incidentaloma is an adrenal mass detected while performing a radiological investigation for another disease. Once an adrenal mass is detected, it is necessary to find out if the mass is benign or malignant to avoid further unnecessary expensive radiological investigations in benign disease (1).
One study showed a mass size of 3 cm or more and exclusive radiocholesterol uptake on scintigraphy has higher chance of excess hormone secretion and should be considered for a more thorough endocrine follow-up (2). One article (published in 2003) mentioned that literature review suggested the prevalence of adrenal incidentalomas to be 2.3% on autopsy and 0.5-2% on CT scan (3). Another study placed the corresponding figures at 8% and 4% respectively (4). Most lesions are histologically adrenocortical adenomas, whereas their prevalence rate is relatively low. The risk of malignancy for benign masses at diagnosis is estimated at about 1/1000 over time, even though increase in size of the masses is noted in 5-25% cases during follow-up (3). Excess hormonal secretion occurs with time in about 1.7% of cases and the risk is higher in adenomas larger than 3 cm (3).
For the purpose of the audit we have followed the European Guidelines where it was mentioned that adrenal adenomas <4cm and radiologically benign needed no further radiological imaging.

According to the European Guidelines, once an incidentaloma is detected the following tests should be undertaken:

(1)To exclude excess cortisol secretion, a 1 mg overnight dexamethasone suppression test at 11 PM should be done (normal: cortisol level the following morning at 9 AM is ≤50 nmol/L or 1.8 μg/dL). However, in patients with a cortisol level of >138 nmol/L (>5 μg/dL) following the test and having no clinical features of Cushings, the term ‘autonomous cortisol secretion’ is used and such patients should be checked for hypertension and type 2 diabetes (1).
In case of overnight Dexamethasone suppression test, the recommendations are (1):
(i)Plasma cortisol < 50 nmol/l- nothing needs to be done
(ii)Plasma cortisol between 51-138 nmol/l- in case of no comorbidities like diabetes, hypertension or vertebral fracture- no surgery or follow up is required. Even If related co-morbidities are present - surgery is rarely required and if surgery is not done, follow up is required
(iii)In case Plasma cortisol is >138 nmol/l, in the absence of co-morbidities, surgery is rarely required; however if related comorbidities are present- surgery is required. In both cases if surgery is not done, follow up is required
(2)To exclude pheochromocytoma, estimation of plasma free metanephrines or urinary fractionated metanephrines is necessary (1)
(3)To exclude primary hyperaldosteronism in patients with co-existent hypertension or unexplained hypokalemia, estimation of the aldosterone/renin ratio is required (1)
(4)Measurement of sex hormones and steroid precursors with radiological investigation is necessary if adrenocortical carcinoma is suspected (1).
(5)Adrenalectomy is the standard procedure for unilateral adrenal tumours with clinically significant excess hormone secretion (1).
(6)If the non-contrast CT suggests a benign adrenal mass with density ≤10 Hounsfield units and is homogeneous and smaller than 4 cm, no further radiological investigation is required (1).
(7)If the adrenal mass is indeterminate on non-contrast CT and the results of the hormonal tests do not suggest significant hormone excess, the multidisciplinary team should consider one of the three options: immediate additional imaging with a different technique, imaging again in 6–12 months (non-contrast CT or MRI), or referral for surgery without delay (1)
(8)Urgent assessment of an adrenal mass is necessary in children, adolescents, pregnant women and adults <40 years of age because of a higher chance of malignancy. MRI rather than CT is recommended in such cases (1).
(9)In patients with a history of extra-adrenal malignancy, FDG-PET/CT, performed while investigating for the underlying malignancy, should replace other adrenal imaging techniques (1).
(10) All patients with bilateral adrenal Incidentalomas should undergo clinical and hormonal assessment similar to those with unilateral adrenal Incidentalomas. In addition, serum 17-hydroxyprogesterone should be done to exclude congenital adrenal hyperplasia, and testing for adrenal insufficiency should be considered if it is suspected clinically or if imaging suggests bilateral infiltrative disease or haemorrhage (1).
Criteria :
(1)Documentation that the non-contrast CT is consistent with a benign adrenal mass (Hounsfield units ≤10) that is homogeneous and smaller than 4 cm
(2)Overnight 1 mg dexamethasone suppression test has been done
(3)Documentation of the result with a morning cortisol level following overnight Dexamethasone suppression test of < 50 nmol/l as normal, between 50-138 nmol/l as possible autonomous cortisol secretion and > 138 nmol/l as definite autonomous cortisol secretion
(4)Whether measurement of plasma-free metanephrines or urinary fractionated metanephrines has been done for pheochromocytoma
(5)Whether aldosterone/renin ratio has been checked to exclude primary hyper-aldosteronism
(6)Whether measurement of sex hormones and steroid precursors has been done
(7)Whether patients with clinically significant hormone excess have been referred for adrenal surgery
(8)Whether further imaging has been avoided in case of adenomas <4 cm and clearly benign
(9)Whether in patients with an indeterminate adrenal mass (by imaging) opting not to undergo adrenalectomy following initial assessment, a repeat non-contrast CT or MRI after 6–12 months has been done or ordered to exclude significant growth.
(10)Whether MRI rather than CT has been done in patients <40 years of age
(11)In bilateral adrenal adenomas whether 17 hydroxy progesterone (for Congenital Adrenal Hyperplasia) has been done together with a Short Synacthen test (in case there is bilateral infiltrative disease or haemorrhage)
(12)If there was any patient with extra-adrenal malignancy and if so, whether FDG-PET/CT, performed while investigating for the underlying malignancy replaced other adrenal imaging techniques.

Results:

17 patients were found who had CT adrenals. Of these 3 patients did not have Incidentalomas and were excluded from the audit
Total number of patients: 14;
Males=5 (36%), Females=9 (64%)
Age in years: 20-30 yrs =1; 40-50 yrs =2; 50-60 yrs =4; 60-70 yrs =3; 70-80 yrs =3; 80-90 yrs =1

(1)Documentation of benign adrenal nodules=11 (79%); indeterminate or suspicious nodules=2 (14%); adrenal metastases=1(7%)
(2)Overnight 1 mg dexamethasone suppression test was done in 7 out of 14 patients (50%); 24 hours Urinary Cortisol was done in 6 out of 14 patients (43%); 1 patient had suspicious nodule on the right adrenal and was referred straight way to the Endocrinal Surgery Department at a Tertiary hospital without any hormonal investigation
(3)Out of 7 patients who had dexamethasone suppression test: 5 patients had cortisol <50 nmol/l; 1 had cortisol 54 nmol/l and 1 had cortisol 61 nmol/l.
(4)24-hours urinary cortisol was normal in all patients in whom it was done
(5)Urinary metanephrines were done in 4 patients; plasma metanephrines were done in 8 patients (Results were normal): Total 12 out of 14 (86%)
(6)Aldosterone/Renin was done in 9 out of 14 patients (64%)
(7)Sex hormones and steroid precursors were requested in 3 out of 14 patients (21%)
(8)1patient was less than 40 years but had CT adrenals instead of MRI scan of adrenals
(9)3 patients out of 14 (21%) had bilateral masses: 1 of them had Short Synacthen Test and 1 early morning Cortisol (very low); none had 17 hydroxyprogesterone test done
(10)1 had extra-adrenal malignancy (lung tumour with adrenal metastases, liver and brain metastases) and had FDG-PET/CT scan
(11)2 patients had indeterminate or suspicious lesions and were referred to Endocrine Surgery Department at a Tertiary hospital. 1 patient is under investigation and the other was subsequently discharged and had interval scans.
(12)Of the remaining 11 patients, 4 were discharged: 1 patient had the 3rd scan 10 months after the 2nd scan and was discharged; 1 patient had the 3rd scan 11 months after the 2nd scan and was discharged; 1 patient had the 3rd scan 2 years after the 2nd scan and was discharged; 1 patient was discharged straight away after normal adrenal scan and normal biochemical hormonal profile.
Summary:
(1)11 out of 14 patients had unilateral adenomas; 3 had bilateral masses. Of these 3 patients, 2 patients had blood tests to check for adrenal insufficiency; 17 hydroxyprogesterone was done in none
(2)2 patients had suspicious or indeterminate unilateral adrenal lesions, they were referred to Endocrine Surgery Department. The patient with Adrenal metastases from Lung Cancer was for palliative treatment
(3)7 out of 14 patients had Dexamethasone suppression test. 6 patients had 24 hours Urine Cortisol measurement.
(4)Measurement of urinary and plasma metanephrines (taken together) was done in 86% cases
(5)Tests for Aldosterone/Renin was done in 64% cases and Sex hormones in 21% cases
(6)The young female patient (28 years) had CT adrenals and not MRI
(7)Altogether 4 patients were discharged
Recommendations:
(1)All patients with adrenal adenomas should have tests for hormone excess such as overnight Dexamethasone suppression test, plasma/urinary catecholamines and renin/ aldosterone
(2)The patients should have sex hormones and steroid precursors measured, particularly in case of suspicious lesions
(3)If the tumours are benign radiologically and there is no evidence of hormone excess, there is no need for further investigations.
(4)If there is evidence of hormone excess, the patients should usually be referred for surgery
(5)All indeterminate lesions should have further imaging and referral for surgery if agreed in MDT
(6)Patients less than 40 years old should have MRI of adrenals
(7)In case of bilateral adrenal lesions, in addition to the biochemical tests done for unilateral adenomas, tests for adrenal insufficiency and measurement of 17 hydroxy progesterone should be done.
References:
(1)Fassnacht M, Arlt W, Bancos I, Dralle H, Newell-Price J, Sahdev A, Tabarin A, Terzolo M, Tsagarakis S, Dekkers OM. Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol 2016 Aug; 175(2):G1-G34. doi: 10.1530/EJE-16-0467
(2)Barzon L, Scaroni C, Sonino N, Fallo F, Paoletta A & Boscaro M. Risk factors and long-term follow-up of adrenal incidentalomas. Journal of Clin Endocrinol and Metab 1999 ; 84: 520–526.
(3)Barzon L, Sonino N, Fallo F, Palu G & Boscaro M. Prevalence and natural history of adrenal incidentalomas. Eur J Endocrinol 2003;149: 273–285.
(4)Favia G, Lumachi F, Basso S & D’Amico DF. Management of incidentally discovered adrenal masses and risk of malignancy. Surgery 2000 ; 128:918–924.

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