Aldosteronism Secondary

Hyperfunction of the adrenal glands occurs in Cushing s syndrome, a disorder caused by excessive secretion of cortisol by the adrenal gland (hypercortisolism). Other causes of adrenal gland hyperfunction include primary and secondary aldosteronism (not discussed in this chapter refer to textbook Chap. 79 for more information on these disorders). 

Nephrotic syndrome is characterized by proteinuria and edema due to some form of glomerulonephritis. The resulting fall in plasma protein concentration decreases vascular volume, which leads to diminished renal blood flow. This in turn causes secondary aldosteronism characterized by Na and water retention and K+ depletion. Rigid control of dietary Na is essential. Therapy of the nephrotic syndrome using a thiazide (possibly with a K -sparing diuretic) to control the secondary aldosteronism, is a useful initial approach to treatment Since nephrotic edema is frequently more difficult to control than cardiac edema, it may be necessary to switch to a loop diuretic (and spironolactone) to obtain adequate diuresis. 

Individuals with chronic liver disease may have disorders of fluid and electrolyte balance, including ascites, edema, and effusions. Alterations of whole body potassium induced by vomiting and diarrhea, as well as severe secondary aldosteronism, may contribute to muscle weakness and can be worsened by diuretic therapy. The metabolic derangements caused by metabolism of large amounts of ethanol can result in hypoglycemia, as a result of impaired hepatic gluconeogenesis, and in ketosis, caused by excessive lipolytic factors, especially increased cortisol and growth hormone. 

These agents are most useful in states of mineralocorticoid excess, due either to primary hypersecretion (Conn s syndrome, ectopic ACTH production) or to secondary aldosteronism (from heart failure, hepatic cirrhosis, nephrotic syndrome, and other conditions associated with diminished effective intravascular volume) (Table 15-4). Use of other diuretics, like thiazides or loop agents, can cause or exacerbate volume contraction and thus intensify secondary aldosteronism. In the setting of enhanced mineralocorticoid secretion and continuing delivery of Na+ to distal nephron sites, renal K+ wasting occurs. Potassium-sparing diuretics of either type may be used in this setting to blunt the K+ secretory response. 

In contrast to patients with secondary aldosteronism (see below), these patients have low (suppressed) levels of plasma renin activity and angiotensin II. When treated with deoxycorticosterone acetate (20 mg/d intramuscularly for 3 days—no longer available in the USA) or fludrocortisone (0.2 mg twice daily orally for 3 days), they fail to retain sodium and their secretion of aldosterone is not significantly reduced. When the disorder is mild, it may escape detection when serum potassium levels are used for screening. However, it may be detected by an increased ratio of plasma aldosterone to renin. Patients are generally improved when treated with spironolactone, and the response to this agent is of diagnostic and therapeutic value. 

Aldosterone Hyperammonaemia acts as an additional stimulus in aldosterone formation, so that a vicious circle is created comprising hyperammonaemia secondary aldosteronism — hypokalaemia hyperammonaemia. 

Hyperammonaemia as well as hypovolaemia and hypokalaemia (especially when caused by diuretics) give rise to secondary aldosteronism, which in turn reinforces hypokalaemia, hypomagnesaemia and zinc deficiency, (s. fig. 15.2) It is clear that additive factors also act as triggers of HE, setting in motion a vicious circle, so that a multiple and complex process results. This may well explain the variety of biochemical, neuropsychiatric and clinical findings in HE. (15, 25,44, 68) (s. tabs. 15.3, 15.5)... 

In cases of severe liver disease or advanced cirrhosis, the occurrence of secondary aldosteronism must always be anticipated and initially rated as an epiphenomenon. Nevertheless, at a certain point, the activated RAAS can act as a signal for a boost to the renal retention of sodium and may intervene in the pathogenesis of ascites. The aldosterone value and the renal excretion of sodium are closely and inversely correlated. Yet a higher aldosterone value is not always accompanied by a reinforced retention of sodium. This is particularly the case if the feedback by means of sodium is ineffective (= escape phenomenon). The refilling of the plasma volume may well lead to normalization of the renin and aldosterone values, yet not to normalization of the sodium excretion. The reduction in increased aldosterone values is usually accompanied by reinforced natriuresis and diuresis - as has been observed after bilateral adrenalectomy. (s. p. 315) Cirrhosis patients with ascites thus usually show a reduced life expectancy if the renin-plasma value is increased, whereas the prognosis is clearly better if the renin value is normal, (for further reference, see 2, 4—6)... 

Kuntz, E. Oedematous hepatitis a special form of acute viral hepatitis due to secondary aldosteronism. Med. Klin. 1975 70 274-278... 

Deficient aldosterone production occurs in conditions other than Addison s disease (Table 51-6). Isolated aldosterone deficiency accompanied by normal cortisol production is seen in patients with (1) inadequate production of renin by the kidney, which leads to secondary aldosterone deficiency... 

High baseline PRA Stimulated response SECONDARY ALDOSTERONISM... 

Treatment of secondary aldosteronism is dictated by etiology. Control or correction of the extra-adrenal stimulation of aldosterone secretion should resolve the disorder. Medical therapy with spironolactone is the mainstay of treatment until an exact etiology can be located. 

Corry DB, Tuck ML. Secondary aldosteronism. Endocrinol Metab Clin North Am 1995 24 511-529. 

As with other K+-sparing diuretics, spironolactone often is coadministered with thiazide or loop diuretics in the treatment of edema and hypertension. Such combinations result in increased mobilization of edema fluid while causing lesser perturbations of K+ homeostasis. Spironolactone is particularly useful in the treatment of primary hyperaldosteronism (adrenal adenomas or bilateral adrenal hyperplasia) and of refractory edema associated with secondary aldosteronism (cardiac failure, hepatic cirrhosis, nephrotic syndrome, and severe ascites). Spironolactone is considered the diuretic of choice in patients with hepatic cirrhosis. Added to standard therapy, spironolactone substantially reduces morbidity and mortality and ventricular arrhythmias in patients with heart failure. 

Factors Other Than Aldosterone That Influence Sodium Excretion Diseases Associated with Disequilibrium of Sodium Metabolism 562 Primary Aldosteronism Secondary Aldosteronism Periodic Paralysis Addison s Disease... 

Secondary aldosteronism results in high blood levels of aldosterone in the absence of a primary adrenal defect. Secondary aldosteronism develops when one of the stimuli of aldosterone secretion is overactive. Consequently, at least three types of conditions can lead to secondary aldosteronism excess of renin, ACTH, or potassium. The condition encountered most often clinically is that in which renin is overproduced because of increased secretion by the juxtaglomerular apparatus or, more rarely, because of overproduction of precursors or extrarenal secretion (for example, by tumors). Renal secretion is stimulated when (1) arterial blood flow to the kidney is reduced (stimulation of baroreceptors), either as a result of the reduction in effective blood volume or renal artery obstruction or (2) osmoreceptors are stimulated as a result of hyponatremia. The arterial blood volume can be reduced by factors that decrease the blood volume (reduced water, sodium, or both), passage of fluid from the blood vessels to the extracellular compartment, and pregnancy (see Table 9-1). 

Table 9-1. Conditions that lead to secondary aldosteronism...

This form of aldosteronism must be distinguished from primary aldosteronism due to adrenal hyperplasia and ordinary secondary aldosteronism. In primary aldosteronism, sodium deprivation results in a reduction of sodium in blood and potassium in urine, potassium retention is facilitated, and, as a result, hypokalemia is corrected. In the juxtaglomerular disease, uri-... 

Most clinical cases of secondary aldosteronism are associated with hypertension or edema. Of course, in hypertension. Starling s law still applies in edema, it does not apply. In either case, persistent hyperaldosteronemia results in sodium retention, which expands the volume of the body fluid by promoting water retention. In hypertension, the expansion concerns mainly the blood volume, and hypertension is aggravated. In edema, the expansion mainly affects the extracellular fluid, and edema is exacerbated. Persistent hyperaldosteronemia in both hypertension and edema leads to hypokalemia with muscle weakness and even paralysis, polyuria, and metabolic alkalosis [33] (see Fig. 9-13). 

The increased sodium-potassium exchange—which is a consequence of (1) the inability to exchange sodium for hydrogen, and (2) the secondary aldosteronism that develops as a result of the decreased ECF... 

Kaplan, N.M. Secondary aldosteronism With observations on the definition of hypokalemia. Amer. J. din. Path. 54, 316-323 (1970)... 

Renin assays can be useful in distinguishing between primary and secondary aldosteronism. It can be measured by its enzymic action on angiotensinogen, the product, angiotensin I, being measured by radioimmunoassay. 

Primary sodium excess. This occurs in primary aldosteronism (Conn s syndrome) when there is an inappropriate secretion of aldosterone. Hypokalaemia, possibly accompanied by hypernatraemia, are features of this condition. Secondary aldosteronism, when aldosterone is secreted in conditions where there is stimulation of the renin-angiotensin system by reduced renal blood flow (e.g. hypoproteinaemic states or cardiac failure), can also be considered as a cause of abnormal sodium metabolism. Hypernatraemia, however, is not a feature of this condition and the plasma sodium level may even be low. 

---