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Guideline: Adrenal incidentaloma

Screening for pheochromocytoma is primarily done █ RECOMMENDATION 9
by measuring plasma-free metanephrines or 24-hour In cases of suspected ACC and/or when clinical signs
urinary fractionated metanephrines, depending on cen- of virilization are present, serum testing for excess
ter-specific testing availability. Plasma normetanephrine androgen should be performed (Clinical principle).
levels >2.2 nmol/L or metanephrine levels >1.2 nmol/L
are highly specific for cathecholamine hypersecretion.
45
A 24-hour urinary metanephrine level two times great- MANAGEMENT OF ADRENAL
er than the upper limit of normal is similarly highly INCIDENTALOMAS
sensitive and specific.
46
Traditionally, it has been recommended that all Cortisol-secreting adrenal lesions
patients with adrenal incidentalomas be tested for It is well-accepted that patients with unilateral cortisol-
pheochromocytomas. Recent evidence from obser- secreting adrenal lesions and clinical signs/symptoms of
vational studies suggests that biochemical testing for Cushing’s syndrome should undergo surgical resection
pheochromocytoma is unnecessary in adrenal inci- of the hypersecreting adrenal gland; 5,51 however, the
dentalomas with unenhanced attenuation of <10 HU optimal management of patients with cortisol-secreting
(adrenal adenomas). 47-49 In the largest of these trials, adrenal lesions without symptoms of Cushing’s syn-
99.5% (374/376) of patients with pheochromocytomas drome is less clear. These patients, historically referred
had unenhanced attenuation of >10 HU upon retro- to as having subclinical Cushing’s syndrome, are now
spective review. The remaining two patients’ masses labelled to have mild autonomous cortisol secretion
were exactly 10 HU, with none displaying <10 HU. (MACS). A recent systematic review, comprised of
Considering this emerging evidence, and the fact generally low-quality observational studies, showed
that biochemical testing for pheochromocytoma can an association between failed cortisol suppression on
be cumbersome, time-consuming, and frequently falsely 1 mg dexamethasone suppression testing and type 2
positive, the panel felt it could be omitted in cases diabetes, hypertension, cardiovascular events, vertebral
when unenhanced CT is clearly in keeping with an fractures, and mortality. Importantly, it also revealed
5
adrenocortical adenoma (HU <10). that across three cohort studies with median followups
ranging from 3–7.5 years, no patients with failed corti-
RECOMMENDATION 8.1 cal suppression progressed to develop overt Cushing’s
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Screening for pheochromocytoma can be omitted in syndrome. Based on this, the panel felt that subclinical
patients who have unequivocal adrenocortical adeno- Cushing’s should be regarded as having a low risk of
mas confirmed on unenhanced CT (HU <10) and progression to overt Cushing’s but can still contribute
no signs or symptoms of adrenergic excess (Weak to medical comorbidity.
recommendation, low-quality evidence). To understand the impact of surgery compared to
conservative management in patients with MACS, a
RECOMMENDATION 8.2 systematic review consisting of one randomized control
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Patients with adrenal incidentalomas that display ≥10 trial (RCT) and three observational studies was con-
5
HU on non-contrast CT or who have signs/symp- ducted. Despite the RCT, the quality of the evidence
toms of catecholamine excess should be screened was downgraded to low-quality given problems with
for pheochromocytoma with plasma or 24-hour uri- confounding, bias, imprecision, and indirectness. None
nary metanephrines (Strong recommendation, moderate- of the studies included in the meta-analysis looked at the
quality evidence). impact of surgery on vertebral fractures, cardiovascular
events, or mortality. The review showed that without
Adrenocortical carcinoma is responsible for more surgery, no patients improved with respect to diabetes,
than half of androgen hypersecretion, which can be hypertension, or dyslipidemia. With surgery, however,
confirmed by testing serum levels of dehydroepiandros- improvements were seen in the rates of diabetes and
terone (DHEA-S), testosterone, 17B-estradiol, 17-OH the severity of hypertension and dyslipidemia. Based
5
progesterone, androstenedione, 17-OH pregnenolone, on this data, the panel felt that adrenalectomy could
11-deoxycorticosterone, progesterone, and estradiol. 50 be an option for select patients with MACS, particularly
those who are young or have progressive metabolic
comorbidities attributable to cortisol excess.

CUAJ • FEBRUARY 2023 • VOLUME 17, ISSUE 2 19