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 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.
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.