Adrenocortical Causes of Hypertension

Primary aldosteronism is the most common cause of secondary hypertension. In the past, screening for primary aldosteronism was offered only in patients with hypertension associated with hypokalemia. Recent studies showed that hypokalemia is seen in only 25% of the patients with primary aldosteronism, which has increased the prevalence of primary aldosteronism to 10–15% of all cases with new onset hypertension. 1. Introduction Approximately 85 million people in the United States are estimated to be hypertensive. In the majority, the hypertension is “essential” or “idiopathic,” but a subgroup of approximately 15% has secondary hypertension. The secondary causes of hypertension can be divided into renal (e.g., renovascular or renal parenchymal disease) and endocrine causes. There are at least 14 endocrine disorders in which hypertension may be the initial clinical presentation (Table 1). Table 1: Endocrine causes of hypertension. A further classification of the adrenocortical causes of hypertension based on the levels of renin and aldosterone can be used for the diagnostic approach of a patient with suspected endocrine hypertension (Table 2). Table 2: Adrenocortical causes of hypertension. An accurate diagnosis of endocrine hypertension provides the clinician with a unique treatment opportunity, that is, to render a surgical cure or to achieve a dramatic response with pharmacologic therapy. Primary hyperaldosteronism, which represents the most common cause of endocrine resistant hypertension, is reviewed here. 2. Aldosterone Biosynthesis and Control of Secretion The differentiation of the adrenal cortex into distinct zones has important functional consequences. The zona glomerulosa comprises approximately 15% of the cortex (depending upon sodium intake). Cells are clustered in spherical nests and are small with smaller nuclei in comparison to other zones. The zona fasciculata comprises the 75% of the cortex; in this zone, the cells are large and lipid laden and form radial cords between the fibrovascular radial network. The innermost zona reticularis is sharply demarcated from both zona fasciculata and the adrenal medulla; cells are irregular with little lipid content. Three main types of hormone are produced by the adrenal cortex-glucocorticoids (cortisol, corticosterone), mineralocorticoids (aldosterone, deoxycorticosterone), and sex steroids (mainly androgens). Aldosterone is synthesized from cholesterol in a series of six biosynthetic steps [1]. The first four steps are also involved in the synthesis of cortisol, whereas the last two pertain only to