Hypokalemic weakness in primary aldosteronism (Conn Syndrome) Hypokalemic weakness because of hypersecretion of the major adrenal mineralocorticoid aldosterone was first described by Conn and associates in 1955. In primary aldosteronism, the cause of the hypersecretion is in the adrenal gland itself, usually an adrenal cortical adenoma, less often adrenal cortical hyperplasia. Although the disorder is uncommon (occurring in approximately 1 percent of unselected hypertensive patients), its recognition is essential for effective treatment. Persistent aldosteronism is frequently associated with hypernatremia, polyuria, and alkalosis, which predispose to attacks of tetany as well as to hypokalemic weakness. Conn and associates (1964), in an analysis of 145 patients with primary aldosteronism, found that persistent muscular weakness was a major complaint in 73 percent; intermittent attacks of paralysis occurred in 21 percent; and tetany in another 21 percent. These manifestations were much more frequent in women than in men, in contrast to the preponderance of men among patients with hypokalemic periodic paralysis of familial type. Rarely, as already noted, primary aldosteronism is produced by the chronic ingestion of licorice; this is due to its content of glycyrrhizic acid, a potent mineralocorticoid (Conn et al, 1968).
The muscle fibers of patients with primary aldosteronism show necrosis and vacuolation. Ultrastructurally, the necrotic areas are characterized by dissolution of myofilaments with degenerative vacuoles; nonnecrotic fibers contain membrane-bound vacuoles and show dilatation of the sarcoplasmic reticulum and abnormalities of the transverse tubular system, suggesting that vulnerability of the latter structures may be responsible for the muscle fiber necrosis (Atsumi et al).
This dramatic syndrome is observed during general anesthesia in susceptible individuals, some of whom clearly have a channelopathy. It is characterized by rapidly rising body temperature, extreme muscular rigidity, and a high mortality rate. Since the original report by Denborough, as larger experience was gained with this entity, it proved in some cases to be a metabolic myopathy inherited as a dominant trait, rendering the individual vulnerable to any volatile anesthetic agent, particularly halothane, and to the muscle relaxant succinylcholine. The fundamental cause in a proportion of cases is an aberration in a component of the ryanodine calcium channel. Malignant hyperthermia has been estimated to occur approximately once in the course of every 50,000 administrations of general anesthesia.
The full clinical picture is striking but anesthesiologists have become adept at detecting its earliest stages and aborting the process. As halothane or a similar inhalational anesthesia is induced, or succinylcholine is given for muscular relaxation, the jaw muscles unexpectedly become tense rather than relaxed and soon rigidity extends to all of the muscles. Thereafter, the body temperature rises to 42çC or 43çC and there is tachypnea and tachycardia. Blood pH may fall to 7 or below. There may be gross myoglobinuria and serum CK reaches extraordinarily high levels. Circulatory collapse and death may ensue in approximately 10 percent of cases, or the patient may survive with gradual recovery. In some cases there is the same sequence of events (increased temperature and acidosis) without muscular spasm. In cases of early death, the muscle may appear normal by light microscopy. With survival for several days, samples of muscle reveal scattered segmental necrosis and phagocytosis of sarcoplasm without inflammation. Patients with a particular congenital myopathy (central core myopathy), and those with King-Denborough syndrome mentioned later, have a propensity to malignant hyperthermia as noted in Chap. 45.