Production of excess aldosterone by adrenal adenomas has been the subject of many articles, one of the earliest and most notable being that of Conn muscular weakness has been observed in 75 percent of the reported cases of hyperaldosteronism. In nearly half of those with muscle weakness there was either hypokalemic periodic paralysis or tetany. Chronic potassium deficiency may express itself either by periodic weakness or by a chronic myopathic weakness. An associated severe alkalosis causes the tetany. As in the weakness of Addison disease, there is no structural disorder of muscle, except perhaps for vacuolation, which is the result of severe hypokalemia.
Diseases of Parathyroid Glands and Vitamin D Deficiency
A proportion of patients with parathyroid adenomas complain of weakness and fatigability. Vicale described the first example of this disorder and remarked on the muscular atrophy and weakness and the pain on passive or active movement. The tendon reflexes were retained. A few scattered muscle fibers had undergone degeneration, but claims for a denervative muscle process are disputed. We have not been impressed with either a myopathy or neuropathy in this disease.
In hypoparathyroidism, muscle cramping is prominent, but there are no other neuromuscular manifestations. In both hypoparathyroidism and pseudohypoparathyroidism—the latter with characteristic skeletal abnormalities and, in some instances, mental slowness—the most important muscle abnormality is tetany. This is a result of low ionized serum calcium, which depolarizes axons more than muscle fibers.
Osteomalacia, as a result of vitamin D deficiency and disorders of renal tubular absorption, often includes muscle weakness and pain as common complaints, similar to those in patients with primary hyperparathyroidism and with uremia (see Layzer for further comment).
More striking than any of the foregoing disturbances, in our view, has been a chronic proximal myopathy in conjunction with hypophosphatemia associated with solitary bone cysts. In two of our patients, removal of the cyst restored serum phosphorus levels and cured the generalized muscle weakness. Also known is an uncommon syndrome of severe hypophosphatemia and generalized bone pain in association with usually benign mesenchymal tumors of soft tissue and bone (oncogenic hypophosphatemia). These tumors express a fibroblast growth factor that induces renal wasting of phosphorous. Hypophosphatemic myopathic weakness has been noted in our and other critical care units, precipitated by hyperalimentation solutions; the onset of weakness can be so abrupt in this circumstance, as to simulate the Guillain-Barré syndrome. The oral administration of phosphates to raise serum phosphorus cures the nonneoplastic cases. Presumably phosphorus depletion limits the phosphorylation reactions and the synthesis of ATP in muscle.
Proximal muscle weakness and atrophy have been recorded as late developments in many acromegalic patients. Formerly thought to be caused by neuropathy, these symptoms in acromegaly have been convincingly shown by Mastaglia and colleagues to be the result of a generalized myopathy. The serum CK is slightly elevated in some cases, and myopathic potentials are observed in the EMG. Biopsy specimens have shown atrophy and reduced numbers of type 2 fibers, but necrosis of only a few fibers. Treatment of the pituitary adenoma and correction of the hormonal changes restores strength. A mild peripheral neuropathy of sensorimotor type has also been reported in a few patients with acromegaly but is far less frequent than carpal tunnel syndrome and other focal entrapments in this disease.
MITOCHONDRIAL MYOPATHIES (SEE CHAP. 36)