Aldosterone-producing adenoma and other surgically correctable forms of primary aldosteronism

Abstract

Surgically correctable forms of primary aldosteronism are characterized by unilateral aldosterone hypersecretion and renin suppression, associated with varying degrees of hypertension and hypokalemia. Unilateral aldosterone hypersecretion is caused by an aldosterone-producing adenoma (also known as Conn's adenoma and aldosteronoma), primary unilateral adrenal hyperplasia and rare cases of aldosterone-producing adrenocortical carcinoma. In these forms, unilateral adrenalectomy can cure aldosterone excess and hypokalemia, but not necessarily hypertension. The prevalence of primary aldosteronism in the general population is not known. Its prevalence in referred hypertensive populations is estimated to be between 6 and 13%, of which 1.5 to 5% have an aldosterone-producing adenoma or primary unilateral adrenal hyperplasia. Taking into account referral biases, the prevalence of surgically correctable primary aldosteronism is probably less than 1.5% in the hypertensive population and less than 0.3% in the general adult population. Surgically correctable primary aldosteronism is sought in patients with hypokalemic, severe or resistant forms of hypertension. Recent recommendations suggest screening for primary aldosteronism using the aldosterone to renin ratio. Patients with a raised ratio then undergo confirmatory suppression tests. The differential diagnosis of hypokalemic hypertension with low renin includes mineralocorticoid excess, with the mineralocorticoid being cortisol or 11-deoxycorticosterone, apparent mineralocorticoid excess, pseudo-hypermineralocorticoidism in Liddle syndrome or exposure to glycyrrhizic acid. Once the diagnosis is confirmed, adrenal computed tomography is performed for all patients. If surgery is considered, taking into consideration the clinical context and the desire of the patient, adrenal vein sampling is performed to detect whether or not aldosterone hypersecretion is unilateral. Laparoscopic surgery for unilateral aldosterone hypersecretion is associated with a morbidity of about 8%, with most complications being minor. It generally results in the normalization of aldosterone secretion and kalemia, and in a large decrease in blood pressure, but normotension without treatment is only achieved in half of all cases. Normotension following adrenalectomy is more frequent in young patients with recent hypertension than in patients with long-standing hypertension or a family history of hypertension.

Figure 1

Prevalence of subjects with an elevated ARR. This figure, derived from the article of Newton-Cheh et al [4], shows the prevalence of an elevated aldosterone to renin ratio (ARR) among subjects with or without hypertension (HTN) in relation to various antihypertensive treatments (Tx): Diu, diuretics; ACEI, angiotensin-converting enzyme inhibitors; BB, beta-blockers.

Figure 2

Algorithm for screening, diagnosis and management of primary aldosteronism. This algorithm, drawn from recent guidelines[3], suggests screening patients with difficult-to-treat or hypokalemic hypertension using the aldosterone to renin ratio (ARR). Patients with a raised ARR undergo confirmatory tests. Adrenal computed tomography (CT) is performed in patients with confirmed PA. Adrenal vein sampling (AVS) is suggested to patients who may have an adrenalectomy, to identify whether or not aldosterone hypersecretion is unilateral.

Figure 3

Screening, diagnosis and management of primary aldosteronism: an alternative algorithm. In this approach[22], PA is identified by the presence of absolute aldosterone hypersecretion, i.e. the combination of a high aldosterone to renin ratio plus a high level of plasma or urinary aldosterone documented from two separate hormonal measurements. HTN: hypertension. ARR: aldosterone to renin ratio. CT: computed tomography. AVS: adrenal vein sampling.

Figure 4

Computed tomography of the adrenals in three patients with primary aldosteronism. Note the moderate hypertrophy of both adrenal glands in A, the presence of a left hypodense nodule (arrow) in B with a thin right adrenal gland, and the presence of bilateral nodules (arrows) in C. All three aspects may coexist with uni- or bilateral aldosterone hypersecretion, which must be confirmed using adrenal vein sampling. In the patient with the computed tomography shown in C, the aldosterone to cortisol ratio was 1.6 in the inferior vena cava, 0.24 in the left adrenal vein and 42 in the right adrenal vein, indicating the presence of a right aldosterone hypersecretion associated with non-secreting left adenoma.

Figure 5

Blood pressure outcome of adrenalectomy in primary aldosteronism. Percentages of patients with hypertension cure following surgery in studies with more than 50 patients. Studies are classified according to the definition used for hypertension cure. One study was discarded[79] because of a large overlap with a more recent study[22]. One study involved patients from two centers as a derivation sample and a validation sample respectively [24]. Due to significant heterogeneity across studies, a random effects model was used to estimate the combined effects.