Adrenocortical
Tumours
Adrenal Cushing’s
syndrome
Adrenal tumours
cause Cushing’s syndrome when they secrete glucocorticoids or their
metabolites. In this situation, ACTH is suppressed (‘ACTH-independent’
Cushing’s syndrome; Chapter 4) and there may be features of
hyperandrogenism with or without virilisation (androgenic alopecia, deepening
of the voice, clitoromegaly) if adrenal androgens are co-secreted by an adrenal
adenoma or carcinoma (Figure 21.1). Severe hirsutism and virilisation,
particularly when associated with a large adrenal tumour (often
>10 cm), strongly suggest an adrenal carcinoma.
For adrenal
adenomas, adrenalectomy, usually undertaken laparoscopically, is curative.
Postoperative hypoadrenalism can occur because of contralateral adrenal
suppression from previously high circulating glucocorticoid levels. This
requires steroid cover with hydrocortisone or prednisolone until the HPA axis
has recovered, which may take many months.
Adrenal carcinoma is
very rare, carrying a poor prognosis, with only 30% patients surviving 5 years.
Where feasible, open surgery aimed at complete tumour resection should be
considered, as this is the only treatment that can offer cure. Patients with
metastatic disease can be treated with a combination of radiotherapy,
chemotherapy and the adrenal-specific cytotoxic agent mitotane.
Primary
hyperaldosteronism
Primary
hyperaldosteronism is caused by either an aldosterone-producing adrenal adenoma
(Conn’s syndrome) or the more common bilateral adrenal hyperplasia. Primary
hyperaldosteronism is the most common form of endocrine hypertension, whereby
aldosterone secretion is inappropriately elevated and independent of the
renin–angiotensin system. Classically, patients present with hypertension and a
hypokalaemic alkalosis (Figure 21.2). Hypokalaemia is not always present,
especially in bilateral hyperplasia. Screening for primary hyperaldosteronism
should be considered in patients with young onset hypertension, refractory
hypertension (>3 anti-hypertensive agents), hypertension with hypokalaemia
and in hypertensive patients found incidentally to harbour an adrenal adenoma.
A random, ambulant aldosterone : renin ratio is the screening method of
choice, but drugs that interfere with the renin–angiotensin system, especially
beta-blockers, may need to be discontinued for a few weeks in advance for
accurate interpretation.
Patients with biochemically
confirmed disease require imaging of the adrenal glands by CT or MRI. Bilateral
adrenal hyperplasia is treated with aldosterone receptor antagonists
(spironolactone or eplerenone). Patients with unilateral adenomas can benefit
from laparoscopic adrenalectomy, which cures hypokalaemia in 100% and
hypertension in 70% of patients. Adrenal vein sampling may be required to
confirm unilateral aldosterone excess.
Adrenal
incidentalomas
The term adrenal
incidentaloma applies to an adrenal mass 1 cm in size which is discovered
unintentionally in the work-up of clinical disorders unrelated to adrenal
disease. Such adrenal nodules are common, with a discovery rate of >4% in
patients over the age of 50 years using CT or MRI (Figure 21.3). Most tumours
are benign and hormonally inactive, but all require work-up to exclude
malignancy and hormone excess (Table 21.1). The likelihood of hormonal
hypersecretion is greater with increasing size of the tumour, with the
exception of aldosterone-producing adenomas, which tend to be small
(<1 cm). The risk of malignancy also increases with size, such that
adrenalectomy is indicated when tumours are >4 cm regardless of
hormonal status. Adrenalectomy is also indicated for tumours showing hormone
excess, although there is some uncertainty surrounding the merits of surgery in
those with low grade cortisol secretion (subclinical Cushing’s syndrome).
The diagnostic
work-up of these tumours should include an unenhanced CT scan: low density
lesions, often expressed in Hounsfield units, support a benign, lipid-rich
adenoma whereas those with higher density are indeterminate and require further
characterisation. Tumours that are vascular, calcified and heterogeneous are
unlikely to be benign incidentalomas. The biochemical work-up should include
measurement of plasma or urinary metanephrines (Chapter 22), plasma
aldosterone : renin ratio and a 1 mg overnight DST (Chapter 4)
to test for phaeochromocytoma, primary hyperaldosteronism and Cushing’s
syndrome, respectively.
